动物造模,药效评价 zi-bio 2024-10-22 682

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

　　Method: Use acetaminophen? After treating liver cells with matrine and oxymatrine, IC50 was detected 24 hours later? Liver cell enzyme content? Pathological morphology? Content of malondialdehyde and glutathione, and detection of apoptosis rate? Using acetaminophen? After treating zebrafish with matrine and oxymatrine for 96 hours, LC50 was detected? Pathological morphology of liver cells? Content of malondialdehyde and glutathione, and detection of apoptosis rate, as well as detection of oxidative stress-related genes zgc: 136383? Expression of apoptosis related genes EIF4EBP3 and zGC: 123120?

　　Result: Matrine and oxymatrine have toxic effects on liver cells, with an IC50 of 5 for matrine. 3 mmol/L, is oxymatrine>19 mmol/L? Does matrine and oxymatrine treat alanine aminotransferase in liver cells? Alkaline phosphatase? Elevated levels of aspartate aminotransferase and lactate dehydrogenase, liver cell swelling, elevated levels of malondialdehyde, decreased levels of glutathione, and increased apoptosis rate (P<0.05)? matrine="" and="" oxymatrine="" have="" toxic="" effects="" on="" with="" an="" lc50="" of="" 0.41="" l="" for="">3.8 mmol/L for oxymatrine? Zebrafish liver cells treated with matrine and oxymatrine showed mild to moderate vacuolization, increased malondialdehyde content and apoptosis rate, and decreased glutathione content (P<0.05)? Sophora flavescens alkaloids downregulate the oxidative stress-related gene zgc-136383 (P<0.05), downregulate the anti apoptotic gene EIF4BP3, and upregulate the pro apoptotic gene zgc-123120 (P<0.05)?

　　Conclusion: The results of in vivo and in vitro 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 cell apoptosis: matrine downregulates the gene zgc: 136383, reduces lipid transport, and activates oxidative stress response; Matrine upregulates the pro apoptotic gene zgc-123120, downregulates the anti apoptotic gene EIF4EBP3, and induces hepatocyte apoptosis?