Cell necrosis refers to the passive death caused by pathology for a long time, such as physical or chemical damage factors, hypoxia andinnutritionAll lead to cellsnecrosis。The membrane permeability of necrotic cells increases, resulting inCell swelling, organelle deformation or swelling, no obvious nucleus at early stagemorphologyChange, and finally cell rupture.Cell lysis will releaseInclusion, and often cause inflammatory reaction;It is often accompanied by the healing processTissue and organFibrosis, formationscar。
Necrosis is cell death induced by extreme physical, chemical or other serious pathological factors. It is pathological cell death.The membrane permeability of necrotic cells increased, resulting in cell swelling, organelle deformation or swelling, no obvious morphological changes in the early nucleus, and finally cell rupture.The necrotic cells lyse and release contents, causing inflammatory reaction;The process of healing is often accompanied by fibrosis of tissues and organs, forming scars.For a long time, the academia has always considered that cell necrosis is a passive process.However, recent studies also suggest that some proteins are involved in the signal regulation of cell necrosis.For example, studies have shown that receptor interacting serine threonine protein kinase-3 (RIP3) may be the key protein determining TNF-a induced cell necrosis.Normally.RIP3, RIP1 and mixed lineage kinase domain like protein (MI. Kl.) form initial necrosis together.Under the induction of TNF-0 [, RIP3 phosphorylates threonine and 358 serine of MLKL at position 357, and then forms activated necrosis to further mediate cell necrosis.These studies show that cell necrosis is also programmed, so it is also called necrosis and apoptosis.
Cell necrosis is an important response of the body to external pathological stimuli. Cells eliminate the impact of pathological stimuli on the body through their own death and inflammatory reaction, but it may also induce the occurrence of related diseases[1]。
Cell necrosis is another way of cell death different from apoptosis.It usually refers to cell death caused by accidental damage to cells, such as chemical factors (strong acid, strong base, toxic substances, etc.), physical factors (high heat, radiation, etc.), biological factors (pathogens, etc.) or pathological stimuli.At this time, the ATP level in the cell drops to the point where the cell cannot maintain its physiological activities, the cytoplasm appears vacuoles, the cell membrane is damaged, and cell contents, including broken organelles and chromatin fragments, overflow, causing inflammation in surrounding tissues.Chromatin does not agglutinate when cells are necrotic, and does not produce 200bp DNA degradation fragments, but randomly degrades without the formation of apoptotic bodies[2]。
Mechanism of cell necrosis
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Human cellsThere are two basic types of death, one death is controlled by cell genes, and it is an autonomous apoptosis that maintains the stability of the internal environment, that is, cell apoptosis;The other is cell necrosis, which refers to cell necrosis in trauma, ischemia, continuous high temperature, toxin andImmune cellCell disintegration during an attack.Cell necrosis and apoptosis are two distinct phenomena of cell death.Cell necrosis is a passive cell death and an irreversible pathological change.Hepatitis B virus infection is the most common cause of hepatocyte necrosis in China.In addition, severe ischemia and hypoxia, insufficient supply of some nutrients (such as choline, methionine or essential amino acids), and poisoning of some poisons such as carbon tetrachloride and phosphorus can cause serious damage to hepatocytes, leading to necrosis of hepatocytes to varying degrees.Its morphological characteristics are organelle swelling, nuclear pyknosis and bleb formation, followed by DNA hydrolysis, bleb rupture, loss of plasma membrane integrity, and release of various enzymes after lysosome rupture, leading to cell autolysis.Spillover secondary to some cellular componentsInflammatory cell、cell factorCytotoxic particles, toxic oxygen free radicals and other inflammatory reactions lead to further damage to surrounding tissues.Therefore, in many liver diseases, hepatocyte necrosis often includes two important parts. In addition to hepatocyte necrosis caused by primary injury factors, there is also hepatocyte destruction caused by secondary inflammatory reaction to cell lysates[3]。
difference
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Cell necrosis and apoptosis
Although the final results of apoptosis and necrosis are very similar, their processes and manifestations are very different.
ApoptosisApoptosis is an active cell death process. Its occurrence is controlled by the program and caused by gradually activating the apoptosis pathway, without inflammation.And necrosis is due to cellsInclusionIt is released out of the cell and causes inflammation.
The difference between apoptosis and necrosis provides new ideas for drug design, screening and tumor treatment.Different drug targets lead to different cell death modes (apoptosis or necrosis).Drugs can induce cells to die in the way of apoptosis, which is not suitable to trigger inflammatory reaction in surrounding tissues, so as to avoid greater damage to patients caused by drugs.The study found that when anti-tumor drugs act on tumor cells at a low concentration, they induce apoptosis of tumor cells. When the drug concentration is increased and exceeds a certain threshold, it will directly cause necrosis of tumor cells or secondary necrosis of apoptotic cells, which indicates that the death mode of cells caused by injury mainly depends on the level of injury. In addition,The threshold required for the response of the same drug to different types of tumor cells at different concentrations and different action times also varies greatly.Therefore, we should screen and apply drugs that can more specifically induce tumor cell apoptosis in tumor treatment, and study their optimal dose and time of administration, so as to improve the therapeutic effect of tumor[4]。
classification
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Acute necrosis
Organisms are caused by sudden damage, such as the damage to human tissues caused by traffic accidentsCellular structureAnd died due to the destruction of.
Chronic necrosis
Chronic necrosis isSlow occurrenceThe death process ofcell deathThe types ofApoptosisIt can be converted to cell necrosis, and this type of cell necrosis is chronic necrosis.
Some studies have shown that cell necrosis is "unsafe"cell deathAnd often lead toplasma membraneRupture, Cellautolysis, causing acute tissue inflammation (for exampleMyocardial ischemiaNecrosis may cause acutemyocardiumInflammation).Cell necrosis often occurs in pathological changes, andApoptosisIt is a normal physiological phenomenon.
our countrySchool of Life Sciences, Xiamen UniversityprofessorHan JiahuaiProfessor found that in some cells, the expression of RIP3 protein is the key to control apoptosis or cell necrosis.If the expression of RIP3 is high, the cells will go to the necrosis path;Low expression of RIP3 leads to apoptosis.
RIP3 is a biological switch that controls cell apoptosis or necrosis.
