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目的:为探讨蛋白激酶C在脂多糖(LPS)诱导的肝细胞毒性中的作用,研究蛋白激酶C抑制剂Ro318220(Ro)对脂多糖诱导的大鼠肝细胞毒性以及对库普弗细胞(KupferCel,KC)释放肿瘤坏死因子(TNF)的影响.方法:大鼠肝细胞(含KC)以LPS刺激24h,以肝细胞培养上清丙氨酸转氨酶(AlaA)活性评价肝细胞损伤.大鼠KC培养上清的TNF活性以杀伤L929细胞结晶紫染色法测定.结果:Ro降低LPS诱导的大鼠肝细胞培养上清AlaA活性升高并抑制LPS诱导的库普弗细胞释放TNF.结论:Ro拮抗LPS诱导的肝细胞毒性,并抑制LPS诱导的TNF释放.
AIM: To investigate the role of protein kinase C in hepatotoxicity induced by lipopolysaccharide (LPS), the effect of protein kinase C inhibitor Ro318220 (Ro) on lipopolysaccharidemediated hepatotoxicity in rat hepatocytes and the effect on Kupffer cells (KupferCel, KC) release of tumor necrosis factor (TNF). Methods: Rat hepatocytes (including KCs) were stimulated with LPS for 24 h, and the activity of alanine aminotransferase (AlaA) in the supernatant of hepatocytes was used to evaluate the hepatocyte injury. The activity of TNF in rat KC culture supernatant was determined by crystal violet staining of L929 cells. RESULTS: Ro decreased the LPS-induced elevation of AlaA activity in rat hepatocyte culture supernatant and inhibited the LPS-induced TNF release by Kupffer cells. Conclusion: Ro antagonizes LPS-induced hepatotoxicity and inhibits LPS-induced TNF release.