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  

Protective effect of 1,3-diphenyl-1,3-propanedione against N-methylformamide-induced acute hepatotoxicity in mice

作　　者：薛茹[1] 王璐[1] 贾凤兰[1] 阮明[1] 张宝旭[1] 

机构地区：[1]北京大学公共卫生学院毒理学系,国家中医药管理局中药配伍减毒重点研究室,北京100191

出　　处：《中国新药杂志》2012年第22期2627-2630,2635,共5页Chinese Journal of New Drugs

基　　金：国家“重大新药创制”科技重大专项(2009ZX09103-007)

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DPPD 50,100,200 mg.kg-1,qd,连续4 d;腹腔注射给予致肝毒性剂量NMF 2 000mg.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(as-partate 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.

关 键 词：1  3-二苯-1  3-丙二酮 N-甲基甲酰胺 急性肝损伤 小鼠 保肝作用 

分 类 号：R965[医药卫生—药理学]