1,3-二苯-1,3-丙二酮对N-甲基甲酰胺致小鼠急性肝损伤的保护作用

摘要

目的:考察1,3-二苯-1,3-丙二酮(DPPD)对N-甲基甲酰胺(NMF)急性肝损伤的保护作用.方法:小鼠经口分别灌胃给予DPPD50,100,200 mg·kg-1,qd,连续4d;腹腔注射给予致肝毒性剂量NMF 2000mg·kg-1；染毒48 h后测定血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、乳酸脱氢酶(lactate dehydrogenase,LDH)和总胆红素(total bilirubin,T-Bil)活性；留取肝脏组织,常规石蜡包埋切片,HE染色,光镜观察肝脏组织病理变化；制备肝匀浆,测定肝组织中还原性谷胱甘肽(GSH)、氧化性谷胱甘肽(GSSG)和丙二醛(malonaldehyde,MDA)含量,计算GSH/GSSG比值.结果:与对照组比较,模型组小鼠血清ALT,AST,LDH和T-Bil水平升高,肝组织GSH/GSSG比值及MDA含量升高,肝组织细胞变性坏死；预防性给予DPPD组ALT,AST和LDH水平明显降低,肝组织GSH/GSSG比值升高,MDA含量降低,肝脏病理损伤明显改善.结论:DPPD可有效抵御NMF对ICR小鼠肝脏的毒性损伤,调动机体抗氧化应激系统为可能的机制.%Objective: To investigate the effect of 1 ,3-diphenyl-1,3-proanedione (DPPD) on N-methyl-formamide ( NMF)-induced hepatotoxicity in ICR mice. Methods: Mice were orally administered with DPPD at doses of 50, 100 and 200 mg·kg-1, respectively, every morning for 4 days before a hepatotoxic dose of NMF 2 000 mg·kg-1 was intraperitoneally injected. At 48 hours after NMF intoxication, the serum enzymes including alanine aminotransferase (ALT) , aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) , and total bilirubin (T-Bil) were measured; and liver histopathologic changes were examined. Results: DPPD dramatically reduced serum ALT, AST and LDH levels. Liver histopathological examination showed that DPPD inhibited NMF-induced liver pathological damage in a dose-dependent manner. Furthermore, DPPD significantly reduced the hepatic lipid peroxidation, and significantly increased glutathione levels after NMF-induced hepatotoxicity. Conclusion; DPPD can effectively protect ICR mice from NMF-induced hepatotoxicity, and reducing oxidative stress might be a part of the protection mechanisms.