Bile acid is an important component of bileFat metabolismPlays an important role in.Bile acid mainly exists in the enterohepatic circulation system and plays a protective role through recycling.Only a few bile acids enter the peripheral circulation.
The driving force for promoting intestinal and hepatic circulation of bile acid isHepatocyteThe transport system of bile acid absorption and secretionbile、CholecystokininInducedgallbladderShrinkagesmall intestinePropulsive peristalsis, active transport of ileal mucosa and blood flowportal veinInflow of.
stayAnimal MedicineMany experts in the world have studied this, and found that bile acid emulsified fat in animal body expanded withlipaseContact area;RegulationPancreatic lipaseAnd the activity of lipoprotein esterase to improve its hydrolysis metabolism of fat;It transports fat in the intestine and promotes fat absorption.In addition, bile acid is regulated byHormone sensitivityThe activity of lipase significantly reduces the catabolism of autologous fat.In conclusion, bile acid can save energy raw materials, improve energy utilization, improve growth performance and slaughter performance, and is a "positive energy" for resource conservation.
Newly synthesized and recycledbileAcid is secreted into the bile duct to prevent high concentration gradient in the liverCholestasis。The active transport of bile acids is an important factor in regulating the formation and flow of bile acids.The secretion of bile acid also highly affects cholesterol, phospholipidsbilirubinSecretion into bile.The osmotic pressure generated by the active transport of bile acids leads to water andelectrolyteThe secretion into the bile duct increases, thus increasing the amount of bile flowing through the bile duct.
Bile acid ingallbladderConcentrated 5-10 times in medium storage.After eating, the gallbladder shrinks under the action of trypsin.During contraction, the gallbladder acts as a motor to drive the enterohepatic circulation.Usually, the concentration of bile acid in the duodenum increases sharply within 30 minutes after digestion.
Physiological function
In the gut, various forms ofbileAcids give full play to their respective physiological functions and determine their own destiny again.Bile acids in the upper part of the intestine are related to the digestion and absorption of lipids.Changes of bile acid in the lower segment of the intestine (i.e. ileum and proximal colon):Intestinal bacteriaTransformation occurs under the action, and most of them are reabsorbed in the original or transformed form in the intestinal mucosa according to the active or passive transport mechanism.Only a small part is discharged with food residues.
The absorption and excretion of bile acid through the intestinal tract are related to two characteristics: solubility and polarity.Under the condition of terminal ileum PH, the six main bile acid salts are soluble, so they are all free acids.When in contact with the absorbing surface, all of these complexes are absorbed.But,Lithocholic acidIts solubility is poor, and it is very difficult to be absorbed.Polarity is mainly determined by two factors, one is nuclearhydroxylThe other is the ionization degree of acid radical,taurineThe ionization degree of the conjugates is high, the ionization degree of glycine conjugates is medium, and the free acid is low.bileThe worse the polarity of acid salt, the easier it is to combine with unabsorbed cellulose or bacteria, and the easier it is to passPassive diffusionAbsorbed.
Regulation of bile acids
Bile acids are regulated by 7αhydroxylaseIts activity regulates the rate of bile acid synthesis.Rats were fed with bile acidαThe activity of hydroxylase and the synthesis of bile acid were significantly reduced, indicating that bile acid could inhibitαThe activity of hydroxylase directly or indirectly inhibits the synthesis of bile acid.Another study found that the bile acid pool of diabetic rats was enlarged, and insulin treatment could reduce the size of the bile acid pool and inhibitαHydroxylase and sterols 12αThe activity of hydroxylase and changes the composition of bile acid.[2]
Hepatointestinal circulation is also an important way to regulate the synthesis of bile acid. After the synthesis of bile acid in the liver, it enters through the bile salt output pumpgallbladderAfter eating, it secretes the human intestinal tract, and bile acid secreted into the intestinal tract is absorbed at the end of the ileum through active transport and passive diffusion, leading to the accumulation of a large amount of bile acid in the body, forming a bile acid pool.Bile acid circulates between the liver and small intestine, averaging 6-8 times a day. In each circulation, about 95% of bile acid is reabsorbed, and only about 5% of bile acid is excreted with feces. The lost bile acid is replenished through the synthesis of bile acid.[2]
Bile acid interacts with FXR as a ligand of FXR, therefore, co synthesis is also regulated by FXR.FXR, as a member of the nuclear receptor family, plays a role in regulating transcription factors.FXR is highly expressed in liver, small intestine, kidney and adrenal gland. Different bile acids have different effects on the activation of FXR. Among them, CDCA is the most effective FXR bile acid ligand.At the initial stage of bile acid synthesis, FXR inhibits the negative feedback loop of bile acid synthesis by participating in the induction of small heterodimer ligands.Small heterodimer ligand interacts with liver receptor analog 1 to form heterodimer, thereby inhibiting 7αHydroxylase, which in turn inhibits bile acid synthesis.Further research found that FXR inducedFibroblast growth factorThe cascade reaction of 15-Jun N-terminal kinase (or the cascade reaction of human fibroblast growth factor 19-JNK) was down regulated 7αHydroxylase, which regulates the synthesis of bile acid.Therefore, the regulation of FXR on bile acid synthesis may be indirect.TGR5 has a wide range of expressiongallbladder, ileum, colon, brown fat and white fatParenchymal cellandRodentExpression in liver.Some bile acids can activate TGR5, such as taurocholic acid andTaurocholic acidTherefore, it is also called bile acid receptor.Previous studies found that compared with wild type mice, the total bile acid level of TGR5 knockout mice was significantly reduced, and the bile acid pool was reduced;Intravenous or oral TGR5 agonist 6αEthyl 23 (S) methylcholic acid (INT777) can increase the content of bile acid in rodents.Compared with normal mice, the gallbladder capacity of TGR5 knockout mice was also significantly reduced, and the difference between the two became more obvious after feeding bile acid.These evidences directly or indirectly reflect the important role of TGR5 in bile acid metabolism.[2]
Reabsorption
1. Active transportation: mainly occurs inileumRemote.In the distal ileum, all types ofbileAcids are transported through this mechanism, but the rate is different, mainly depending onhydroxylThe number of bile acids, and whether bile acid molecules are bound or free.
2. Passive transport: mainly in the small intestine and colon.This passive and selective reabsorption rate depends on the ionization degree and polarity of bile acids.The glycine conjugate of unconjugated bile acid and dihydroxybile acid (in the form of non ionization) is also reabsorbed by simple diffusion.This non ionized diffusion through the small intestine membrane can be found in any part of the small intestine andcolonhappen.
Venous transport
Intestinal absorptionbileThe acid is transported back to the liver through the portal vein.In the liver, most bile acids are absorbed.When portal vein blood passes through the liver, about 80%~90% of bile acid can be absorbed at one time.This efficient elimination of bile acids by the liver keeps the concentration of bile acids at a low level.When the concentration of bile acid in portal vein blood increases, bile acidSystemic circulationThe discharge of is increased.Within 1-2 hours after digestionSerum bile acidThe level is about twice higher than that on an empty stomach.
Quantitative characteristics
Healthy adultsbileThe acid storage capacity is about 3~4g.The bile acid reservoir circulates about 8-12 times a day, mainly after meals.The amount of bile acid synthesis in the human body is about 0.4~0.6 g per day, which is used to compensate for the loss of bile acid caused by fecal excretion.This synthesis process consists ofprimary bile acid 7 of the first step of synthetic pathwayα－The negative feedback mechanism of hydroxylase reaction can also be regulated by the rate of cholesterol synthesis.
Interruption of enterohepatic circulation usually results in a significant increase in bile acid synthesis, although the liver has very limited capacity to compensate for bile acid loss.
function
1. Promote the digestion and absorption of lipids
bileHydrophilichydroxylAnd carboxyl groups, and hydrophobic methyl and hydrocarbon nuclei.At the same time, the spatial coordination of hydroxyl and carboxyl groups are allαTherefore, the main configuration of bile acid has hydrophilic and hydrophobic sides, which makes the molecule have the characteristics of interfacial active molecules and can reduce thesurface tensionPromote lipid emulsification.
2. Inhibit cholesterol precipitation in bile（stone）
Bile acid can also prevent gallstone formation.Cholesterol is insoluble in water and is discharged with bilegallbladderDuring storage, bile is concentrated in the gallbladder and cholesterol is easy to precipitatelecithinIt can disperse cholesterol to form soluble microparticles and is not easy to precipitate to form stones.
The physiological functions of bile acids can be summarized as follows: effects on bile secretion;Effect on lipid absorption;Effect on colon function.
Secretory effect
bileThe active transport of acid to bile can promote the excretion of water and solute.Cholesterol andlecithinThe secretion of bile acid is largely dependent on the secretion of bile acid.Bile acids and lecithin play an important role in maintaining cholesterol levels in bile.
The interruption of intestinal hepatic circulation may cause the decrease of bile acid/cholesterol and lecithin/cholesterol ratio in bile.At this time, the bile is cholesterol supersaturated.Cholesterol solubility and cholesterol gallstone formation are closely related to the size of circulating bile acid pool.
metabolism
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bileAcids help emulsify fat and enhancepancreasIt can improve the solubility of lipids by forming mixed colloidal particles and promote the absorption of lipids in the intestine.The important role of bile acid in fat absorption is due toFatty dysenteryAnd cause intestinal tractBile saltSymptoms of decreased concentration, such as bile obstructioncirrhosisAnd taking bile acid combined with drugs.
Bile acids and lipid metabolism
Bile acids play an important role in regulating lipid metabolism.Bile acids not only participate incholesterolAdjustment, andTriacylglycerolIt has been reported that cholesterol receptor coactivating protein knockout mice have functional defects in bile salt output pump, which will lead to malabsorption of triacylglycerol.The rate of bile acid synthesis is related to the increase of blood plasma triglyceride level in patients with hyperlipidemia.Bile acid multivalent chelating agent can increase the synthesis of bile acid and triacylglycerol.CDCA treatment can reduce the level of triacylglycerol in plasma of hyperlipidemia loyalists.Bile acid can regulate the metabolism of triacylglycerol through different mechanisms, including the activation of FXRa mediated by bile acid and the regulation of TGR5.Bile acid is the natural ligand of FXR, which participates in the regulation of lipids through a variety of mechanisms, including the regulation of triacylglycerol and lipoproteins.It is reported that the level of triacylglycerol in high-fat fed FXR knockout mice is significantly higher than that in the control group, and the level of triacylglycerol in the FXR agonist group is significantly lower than that in the control group.Some articles point out that FXR can inducePeroxisome proliferator activated receptorAnd pyruvate dehydrogenase kinase expression, inhibit pyruvate dehydrogenase and increase fatty acid oxidation.FXR agonists can significantly improve hypercholesterolemia in ob/ob mice and db/dh mice.All these suggest that bile acid has the effect of regulating lipid metabolism.Bile acids can also activate TGR5.TGR5 is the first seromembrane bound G-protein coupled bile acid receptor confirmed.Male and female TGR5 knockout mice fed a high-fat diet for 8 weeks developed liver fat and led to an increase in liver triglyceride levels in female mice, while TGR5 agonist 6αEthyl 23 (S) methylcholic acid can reduce the level of plasma triacylglycerol, which indicates that TGR5 has the role of regulating lipid metabolism, and bile acid also plays an important role in lipid metabolism.[2]
Cholesterol relationship
1．bileAcid isCholesterol metabolismIt provides an important excretory pathway.One third of cholesterol catabolism is achieved through bile acid synthesis.
2. Absorbed bile acid can self synthesize bile acidnegative feedback regulationTherefore, it also plays a negative feedback regulation role in the decomposition of cholesterol.
3. Bile acid can promote the secretion of cholesterol in bile and play an important role in maintaining the solubility of cholesterol.
4. Bile acid is necessary for the absorption of cholesterol in the intestine.
6. Bile acid can regulate the synthesis of intestinal cholesterol.
Bile acid and glucose metabolism
Bile acids regulate glucose metabolism through different mechanisms.Research shows that,Type 2 diabetesThe postprandial plasma bile acid level of patients was significantly higher than that of patients with normal blood glucose.Insulin inhibits rate limiting enzyme 7 of bile acid synthesisαHydroxylase, thus reducing the synthesis of bile acid;Glucose stimulates 7αHydroxylase, thereby increasing the synthesis of bile acids.Taurine boundUrsodeoxycholic acidIt can improve the insulin sensitivity of obese people, and the chelating agent of bile acidColeenamineIt can reduce the plasma glucose level, urine glucose excretionglycosylated hemoglobinHorizontal.The glycosylated hemoglobin, plasma fructosaminePostprandial blood glucoseLevel andFasting blood glucoseAll significantly decreased.Bile acid binding resin can also stimulate diet induced ratsGlucagonThe expression of proinsulin and glucagon like peptide 1 precursor increases insulin secretion, reduces blood glucose level and improves insulin sensitivity.Treatment of human hepatoma cells with CDCA canPhosphoenolpyruvateThe expression of carboxylase, glucose 6 phosphatase and fructose 1,6-bisphosphatase decreased.These three enzymes areGluconeogenesisAnd the total bile acid level was negatively correlated with the postprandial 2h blood glucose level, which indicated the role of bile acid in glucose metabolism.
The role of bile acid in glucose metabolism may be mediated by FXR.Murine pancreaticβFXR exists in cells, and bile acid can stimulate pancreas to secrete insulin.It is reported that obechoic acid (a non sterol FXR ligand) can improve the liver and peripheral glucose intake, andInsulin sensitivity27。When FXR is activated by bile acid, the plasma glucose level drops, accompanied by gluconeogenesisgene expressionDown.FXRGene knockout miceIt showed mild glucose intolerance and insulin insensitivity, and the FXR agonist GW4064 could improve theinsulin resistance 。Recent research reports indicate that aldehyde ketone reductase 1B7, a new target of FXR, is a gene related to detoxification, and its overexpression reduces the expression of plasma glucose level, gluconeogenase and lipogenase.Studies have proved that mouse fibroblast growth factor 15 and human fibroblast growth factor are targets of FXR, and these growth factors inhibit cAMP regulatory element binding protein and down regulatePeroxisomesProliferator activation suspendedγCoactivator x inhibits gluconeogenesis induced by eating.These studies suggest that FXR may reduce blood sugar by inhibiting gluconeogenesis, thusCarbohydrate metabolismPlay an important role in.The role of bile acids in glucose metabolism may also be mediated by TGR5.Resins and bile salt transporter inhibitors can inhibit the absorption of bile acids in the ileum, and can also stimulate the release of colon glucagon like peptide 1 through TGR5.Bile acid/colevelen complex can also activate TGR5 in colon, thus promoting the secretion of glucagon like peptide 1, and affecting the expression of TGR5 in glucose metabolismtransgenic miceIt significantly improved the abnormal glucose tolerance of high fetal feeding.The TGR5 agonist 6A-Ethyl23 (S) methylcholic acid could improve the insulin sensitivity of mice, but could not improve the insulin sensitivity of TGR5 deficient mice.[2]
Bile acid and obesity
Bile acids are also linked to obesity.The study found that the level of bile acid in the obese rat model caused by high-fat diet was significantly reduced, and the clinical study on the improvement of obesity induced by high-fat diet after the administration of bile acid in mice also pointed out that although the levels of free bile acid and conjugated bile acid in obese people were slightly lower than those in the apparently normal control, the levels of glycine in obese peopleChenodeoxycholic acidHowever, the level of deoxycholic acid of taurine and taurine goose is higher than that of the control, indicating that obesity will affect the composition of bile acid.There is also evidence that TGR5 is involved in the regulation of energy metabolism in brown adipose tissue. The activation of TGR5 signaling pathway in brown adipose tissue can increase the expression of several mitochondrial genes involved in energy consumption and induce the expression of type 2 deiodinase gene, thus increasing energy consumption and avoiding obesity and insulin resistance.Bariatric surgeryIt can increase the transport of bile acid to the intestinal tract. For example, the liver lipid level of patients after Roux-en-Y gastric bypass surgery is significantly reduced, and the sensitivity of liver insulin is improved.
In conclusion, data from both humans and animals have proved that bile acids play an important role in controlling glycolipid metabolism and body mass, and they are also important signal molecules regulating glycolipid metabolism and body mass.Bile acid metabolism is mainly determined by nuclear receptors FXR andG protein coupled receptorTGR5 mediated.However, the specific mechanism of this effect is still unclear. Therefore, further research should be carried out on bile acid, FXR, TGR5 and weight loss surgery in order to provide better methods to treat obesity, insulin resistance, type 2 diabetes and other metabolic disorders, so as to treat them more effectivelyMetabolic syndrome。[2]
Bile acid and immune response
Bile acid (BA) inImmune cellA variety of cells play an important role in the immune response to external viruses.After the relevant bile acid signal flow of experimental mice is blocked, the antiviral ability can be reduced and the mortality can be increased to varying degrees. The molecular mechanism can be summarized as follows:
After the virus enters the cell, it can quickly activate the NF kB signal axis at a very early stage, promote the transcription factor p50/p65 to translocate into the nucleus through the nuclear pore complex, interact with related genes, promote the transcription of bile metabolism related transport protein SLCO1A2 and key rate limiting enzymes of the reaction chain, such as CYP7A1, CYP7B1, CYP27A1, etc. SLCO1A2 promotes the transport of BA from the outside of the cell to the inside of the cell,Then several rate limiting enzymes participate in cholesterol metabolism pathway to produce BA.
BA binds to TGR5 in the cell and passes through TGR5-GRK-β-Arrestin interaction promotes self phosphorylation of SRC protein, which makes SRC activated.Subsequently, SRC activates a variety of downstream immune response related proteins through phosphorylation modification, including RIG-1, VISA, STING, TBK1, and IRF3. IRF3 is activated and translocated into the nucleus as a transcription factor to promote the expression of downstream interferon INF and activate the immune response.
This mechanism and signal axis suggest that bile acids may have clinical potential for antiviral therapy.
Clinical significance
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1. Liver and gallbladder diseases
2. Gastrointestinal diseases
3. CausebileOther diseases with changes in acid metabolism
When studying the interference of various diseases on bile acid metabolism, biological samples are often strictly classified and separated, and each bile acid component is studied in detail by chromatography.However, in clinical practice, in most cases, such as screening for liver diseases, onlyTotal bile acidA simple enzymological assay was performed to determine the level of the serum albumin.This chapter will focus on the influence of serum total bile acid on liver system diseases, and briefly discuss the pathological level of total bile acid in stool, bile, intestinal extracts and other samples observed clinically.
When acute hepatitis occurs, serumbileThe acid concentration rises sharply.In general, the bile acid that rapidly rises and reaches the peak at the initial stage of the disease almost returns to the normal level at the same time as ASAT.However, compared with other clinical test indicators, the recovery of bile acid level to normal is relatively slow and gradual.
Several studies have confirmed that serum total bile acid is valuable for tracking and detecting viral hepatitis.stayAcute viral hepatitisRehabilitation period, postprandial serumTotal bile acidLevel is the most sensitive indicator.If the concentration of serum total bile acid after meal continues to rise, it indicates thatViral hepatitisIs going tochronic hepatitisConversion.For inAcute hepatitisThe long-term increase of serum bile acid level in patients in rehabilitation period indicates that patients may have serious liver injury, which requires careful tracking and monitoring, and may require liver biopsy.
2. Chronic hepatitis
Since conventional liver examination is relatively insensitive to the conclusion of chronic hepatitis, it is necessary to evaluate chronic liver diseases (chronic persistent hepatitis, chronic hepatitisActive hepatitis、cirrhosis）The severity must be detected and analyzed histologically.However, clinical studies in recent decades have shown that serumbileInstinct level can be used as a sensitive index to detect liver injury in chronic hepatitis.The study confirmed that the concentration of serum total bile acid can be used to distinguish active and inactive hepatitis.The determination of serum bile acid also helps tochronic hepatitisThe therapeutic monitoring can replace the need for repeated liver biopsy experiments.
3. Liver cirrhosis
In patients with liver cirrhosis, due to the decrease of bile acid storage, the concentration of serum bile acid increased, and the excretion of sulfated bile acid in urine increased.Patients with severe cirrhosis, due to functionalHepatocyteThe amount of bile acid decreased, which inhibited the ability of bile acid synthesis.However, the decrease of bile acid storage in patients with moderate cirrhosis may be caused by the deficiency of bile acid synthesis regulation.cirrhosisAlthoughbileThe total amount of acid synthesis decreased, but the level of serum bile acid still increased, which may be related to liver cell damageHepatoparenchymal cellsQuantity reduction andPortal vein systemAnd other factors.
The serum bile acid concentration increased in different stages of cirrhosis, but it was most obvious in the late stage of cirrhosis.
Some patients with cirrhosis, althoughbilirubin, transaminasealkaline phosphataseThe serum bile acid level remained normal, but the serum bile acid level increased significantly.
When the activity of liver cirrhosis decreases to the minimum and other routine liver functions return to normal, the concentration of serum bile acid often remains elevated, so the level of serum bile acid can be used for clinical detection of patients with liver cirrhosis at low activity stage.
4. Alcoholic liver disease
Usually, the serum of patients with alcoholic liver diseasebileThe acid concentration increased significantly.Compared with patients with moderate alcoholic liver disease with mild morphological damage, patients with severe liver damage, such asAlcoholic hepatitisThe concentration of bile acid in patients and serum increased more significantly.
The latest research results show that compared with other conventional liver function detection methods such as enzyme detection, lactose reduction test and BSP detection, the information obtained by serum bile acid determination on the degree of liver injury in patients with alcoholic liver disease is more sensitive and reliable.Serum bile acid andβ-The hexosaminidase combination assay is now recommended as a valuable method to evaluate alcoholic liver disease.
5. Cholestasis
It has been found that the quantitative determination of serum bile acid can be used as a sensitive and specific method to detect cholestasis.When extrahepatic bile obstruction occurred, serum bile acid concentration increased significantly.Most intrahepaticbileStasis patients, such asAcute hepatitisPrimary bilecirrhosisInfant cholestasis, pregnancy cholestasisliver cancerThe serum bile acid concentration of patients with benign recurrent intrahepatic cholestasis was significantly increased.
When bile obstruction occurs, the secretion of bile decreases, and the distribution of bile acid storage is rapidly changed, making serum andurineThe concentration of bile acid increased significantly.
It has been found that alkaline phosphatase, 5i nucleotidase andγ-GlutamyltransferaseIts activity also increased significantly.The mechanism of the increased activity of these enzymes during bile obstruction is still unclear.The most likely mechanism is that when cholestasis occurs, these membrane binding enzymes in the liver produce induction, and then filter the microtubule membrane under the action of bile acid.
The serum bile acid level peaked rapidly after the occurrence of biliary obstruction, and remained basically unchanged during the long-term obstructive process thereafter.On the contrary,bilirubinHorizontallybileSlowly rise during blocking.Serum alkaline phosphataseThe activity increased irregularly, and there was great difference among individuals.
After the extrahepatic bile acid obstruction was relieved by drainage, the serum bile acid level decreased rapidly.andserum bilirubin , alkaline phosphatase andγ-The activity of glutamyltransferase and others slowly returned to normal during external drainage.
However, serumTotal bile acidThe determination seems to have little effect on the differential diagnosis of intrahepatic and extrahepatic cholestasis.
6. Initial biliary cirrhosis
Initial biliary cirrhosis is a cholestasis disease, and the liver parenchyma damage may be the smallest at this time. Routine liver function testing can only find slight changes.For most patients with primary bile acid cirrhosis, the serum bile acid level is significantly increased, so it can be used as a valuable diagnostic indicator to evaluate this disease.In the early stage of biliary acid cirrhosis, although the fasting serum bile acid may still remain within the normal range, the postprandial bile acid level is abnormally elevated, indicating that biliary cirrhosis has indeed occurred.
In uncomplicated pregnancy, the serum total bile acid level is always within the normal range, although with the passage of pregnancy, the CDCA level often increases.
However, the serum bile acid level increased significantly when pregnant cholestasis occurred.Therefore, the determination of bile acid is helpful to differentiate between cholestatic pruritus and non cholestatic pruritus.
Other test indicators, such asγ-GT, bilirubin, alkaline phosphatase, etc. often fluctuate during normal pregnancy. Therefore, in these cases, serum bile acid has important diagnostic value.
8. Pediatric liver disease
Due to immaturitybileThe level of serum bile acid in neonates was significantly higher than that in adults.happenNeonatal hepatitisAnd all kinds of pediatric cholestasis, the level of fasting bile acid in patients increased sharply.However, serumTotal bile acidSimilar family is not enough to differentiate and diagnose various neonatal liver and gallbladder diseases.The determination of each bile acid component can not only provide etiological indications for neonatal hepatitis and other different types of pediatric cholestasis, but also help politicians track and monitor the progress, pathological activity and treatment response of such diseases.
9. Toxic liver disease
It has been confirmed that frequent exposure to hepatocyte toxic substances can cause acute or chronic liver injury.Some industrial organic solvents, such ascarbon tetrachloride、TetrachloroethaneIt has serious damage to hepatocytes.
Due to the increasing variety of potential hepatotoxic substances in the environment, the clinical laboratory urgently needs sensitive screening methods to detect occupational and non occupational visceral diseases early.
Most routine liver function test indicators, such astransaminase、γ-Glutamyltransferase is extremely insensitive to the early diagnosis of toxic liver diseases.However, serumbileThe determination of acid is very valuable for the detection and screening of mild liver diseases caused by hepatotoxic substances.
A recent study showed that among the 23 workers who were exposed to polyethylene, 11 workers had significantly increased serum bile acid levels, and only 3 workers had significantly increased liver enzyme indicators.The detection results of occupational workers exposed to vinyl chloride showed that the level of fasting serum bile acid could be a sensitive indicator of early liver injury.
The determination of serum bile acid is of great value in detecting the liver injury of patients with acute hepatotoxic drug poisoning and tracking the liver function of such patients.In terms of detecting the therapeutic dose effect of hepatotoxic drugs, serumTotal bile acidLevel is also an important test indicator.
It has been found that,bileAcids consist ofduodenumReflux to the stomach plays an important role in the pathogenesis of gastric ulcer.It has been proved that bile acid can causegastric mucosaInjury, and bile acid reflux promotes gastric developmentcancerationeffect.
Under normal circumstances, there is no bile acid in gastric juice, and gastric acid will not change bile acid.Therefore, in gastric extractsTotal bile acidThe measurement of serum level can be used as a valuable diagnostic index for the diagnosis of duodenogastric bile reflux, and can provide important information in the clinical detection process of patients undergoing gastric surgery.
2. Intestinal Stasis Syndrome
The main characteristics of the small intestinal turbid syndrome are diarrhea caused by the overgrowth of small intestinal bacteriaFatty dysentery、Vitamin B12Obstruction of absorption.
Small intestinal bacterial overgrowth,bileAcid metabolism changed significantly.The degradation rate of bile acid increased significantly, resulting inUnconjugated bile acidThe level rises sharply.
3. Small enteritis disease (segmental ileitis)
In patients with segmental ileitis, bile acid metabolism changes with the injury of ileitis.SegmentalityileumInflammation leads to the loss of ileal mucosal function, bile acid absorption disorder and diarrhea. As a result, the excretion of bile acid in the stool of patients increases, and the total storage of bile acid in the body decreases.
The ileal function of patients with segmental ileitis was studied by measuring the response of serum bile acid concentration to meal stimulation.The results showed that the postprandial blood bile acid level could be used as an important indicator for the diagnosis of segmental ileitis.
The level of fasting bile acid in patients with segmental ileitis often remained normal or dropped to a certain level, but the level of bile acid decreased significantly after eating, indicating that the absorption function of the small intestine decreased.
Since segmental ileitis is closely related to liver disease, if the level of serum bile acid in patients with segmental ileitis increases, it indicates that patients may have liver function damage.
The epidemiological comparative study on people with different risk of colon cancer shows that colon disease is closely related to diet habits and geographical location. It has been noted that the incidence of colon cancer is greatly increased in people whose diet is rich in animal fat and protein but low in cellulose.
In 1969, ARIES et al. speculated that colon cancer was due to the decomposition of some benign colonic bacterial florasubstrateCaused by the metabolites produced.Based on this assumption, people believe thatbileAcid is associated with intestinal carcinogenesis.
Statistical data show that patients with ulcerative colitis, adenomatous polyps, and familial polyposis have a significantly increased risk of colon cancer. Therefore, for decades, the bile acid metabolism of patients with these diseases has increasingly aroused people's interest.Compared with normal people, the level of fecal bile acid in patients with benign adenoma was significantly higher, the total amount of bile acid metabolism and the colonicDeoxycholic acidThe absorption capacity of is also greatly improved.
Many studies have confirmed that there is a significant correlation between the level of fecal bile acid and the incidence of colon cancer.However, further research is needed to clarify the role of bile acid in the process of colorectal carcinogenesis and the relationship between the elevated level of fecal bile acid and the risk of colon cancer.
On August 30, 2012, researchers found that if drugs could be used to secretebileAcid is forced out of the body, promoting the secretion of new bile acid, which may improvediabetessymptom.
Gallbladder effect
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The gallbladder is a pear shaped pocket structure attached to the liver and opened in the extrahepatic bile ductbileTherefore, it is called gallbladder.Bile is produced by hepatocytes and discharged into the intestinal tract through intrahepatic and extrahepatic bile ducts to help digestion of food and absorption of nutrients.
