动物造模 z-bio 2022-09-20 357

　　Objective: To compare the hepatotoxicity of matrine and oxymatrine, to explore the severity and characteristics of their toxicity, and to preliminarily clarify the toxicity mechanism?

　　Methods: Hepatocytes were treated with acetaminophen (APAP), matrine and oxymatrine. After 24 hours, IC50, enzyme content of hepatocytes, pathological morphology, malondialdehyde (MDA) and glutathione were detected. The content of glutathione (GSH) and the rate of apoptosis were detected? Zebrafish were treated with acetaminophen, matrine and oxymatrine, and after 96 h, LC50, pathological morphology of hepatocytes, malondialdehyde and Glutathione content, and the apoptosis rate, and the expression of oxidative stress-related genes zgc: 136383? Apoptosis-related genes EIF4EBP3 and zgc: 123120?

　　Results: Matrine and Oxymatrine had toxic effects on hepatocytes, the IC50 of matrine was 5.3 mmol/ L, and Oxymatrine was > 19 mmol/ L? Matrine and Oxymatrine treated hepatocytes 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 have toxic effects on zebrafish, the LC50 of matrine is 0.41 mmol/ L, and oxymatrine is > 3.8 mmol/ L? Zebrafish hepatocytes treated with matrine and oxymatrine showed mild to moderate vacuolation, increased malondialdehyde content and apoptosis rate, and decreased glutathione content (P < 0.05)? Matrine down-regulated the oxidative stress-related gene zgc:136383 (P < 0.05), Down-regulation of the anti-apoptotic gene EIF4BP3 and up-regulation of the pro-apoptotic gene zgc: 123120 (P < 0.05)?

　　Conclusion: The results of the in vitro and in vivo models are consistent. Matrine and oxymatrine have liver toxicity, and their toxicity characteristics are similar. The toxicity of matrine is greater than that of oxymatrine? The mechanism of liver toxicity is related to oxidative stress and apoptosis: bitter Sampling down-regulates the gene zgc: 136383, reduces 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?