肝毒性 z-bo 2020-12-06 450

　　Objective: To compare the liver toxicity of matrine (MT) and oxymatrine (OMT), to explore the severity and characteristics of their toxicity, and to clarify the mechanism of toxicity initially? Methods: Hepatocytes were treated with acetaminophen (APAP), matrine and oxymatrine. After 24 hours, IC50, liver cell enzyme content, pathological morphology, malondialdehyde (MDA) and malondialdehyde (MDA) were detected. The content of glutathione (GSH) and the detection of apoptosis rate. Zebrafish were treated with acetaminophen, matrine and oxymatrine. After 96 hours, the LC50, pathological morphology of hepatocytes, malondialdehyde and oxymatrine were detected. Glutathione content, and detect the apoptosis rate, and detect the expression of oxidative stress-related genes zgc: 136383? Apoptosis-related genes EIF4EBP3 and zgc: 123120? Results: Matrine and oxymatrine are toxic to hepatocytes. The IC50 of matrine is 5.3 mmol/L, and the value of oxymatrine is> 19 mmol/L. Matrine and oxymatrine are treated with liver cells. The content of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase and lactate dehydrogenase increased, liver cells swelled, malondialdehyde content increased, glutathione content decreased, and apoptosis rate increased (P<0.05)? matrine="" and="" oxymatrine="" are="" toxic="" to="" zebrafish.="" the="" lc50="" of="" is="" 0.41="">3.8 mmol/L? Zebrafish liver cells treated with matrine and oxymatrine Shows mild to moderate vacuolation, increased malondialdehyde content and apoptosis rate, and decreased glutathione content (P<0.05)? Matrine down-regulated oxidative stress-related genes zgc: 136383 (P <0.05), Down-regulate the anti-apoptotic gene EIF4BP3 and up-regulate the pro-gene zgc: 123120 (P <0.05)? Conclusion: The results of in vivo and in vitro models are consistent. Matrine and oxymatrine have hepatotoxicity, and their toxicity characteristics are similar. The toxicity of matrine is greater than oxymatrine? The mechanism of liver toxicity is related to oxidative stress and apoptosis: Matrine Phenine down-regulates the gene zgc: 136383 to reduce lipid transport and activates oxidative stress; matrine up-regulates the pro-apoptotic gene zgc: 123120, down-regulates the anti-apoptotic gene EIF4EBP3 and induces hepatocyte apoptosis?