摘要:
目的 探讨不同作用方式的甲氰咪呱对非酒精性脂肪性肝炎(NASH)大鼠的作用.方法 雄性SD大鼠40只,随机分为4组,即:对照组、模型组、甲氰咪呱治疗组、甲氰咪呱预防组.对照组普通饲料喂养,模型组喂高脂饮食,甲氰咪呱治疗组在高脂饮食12周后给予甲氰咪呱200 mg·kg-1·d-1)灌胃治疗,甲氰咪呱预防组给予高脂饮食同时进行甲氰咪呱200 mg·kg-1·d-1灌胃.16周末处死各组大鼠,测定血清转氨酶(ALT、AST)及血脂(TG、TC)、血清TNF-α;光镜下观察肝脏组织病理形态学改变,测定肝组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性.结果 与对照组比较,模型组ALT、AST、TG、TC显著增高(P<0.05),甲氰咪呱治疗组及预防组较模型组降低(P<0.05),且预防组AST与治疗组比较有显著差异(P<0.05);与对照组比较,模型组MDA及血清TNF-α显著增高,SOD活性下降(P<0.05);甲氰咪呱治疗组及预防组与模型组比较,MDA显著降低,SOD活性升高,均有显著差异(P<0.05);与对照组比较,模型组肝脏脂肪变性程度和炎症活动度均显著增高(P<0.05);与模型组比较,甲氰咪呱治疗或预防给药均可促进上述指标恢复(P<0.05).结论 甲氰咪呱对高脂饮食诱导的大鼠NASH有一定治疗效果,其有效阻遏了自由基引发的氧化应激,保持了氧化/抗氧化平衡,改善NASH大鼠脂肪变性,减轻炎症反应,且甲氰咪呱预防组的效果优于治疗组,说明对NASH的早期治疗更有益于NASH的转归.%Objective To investigate effects of the different mode of action of cimetidine on nonalcoholic steatohepatiffs (NASH) rats. Methods Forty male rats were randomly divided into control group (ordinary diet), model group (high-fat diet), cimetidine treatment group (intragastric administration with cimetidine 200 mg/kg per day, after feeding high-fat diet 12 weeks), cimetidine prevention group (intragastric administration with cimetidine 200 mg/kg per day, beginning with feeding high-fat diet). The rats in every group were killed at 16 weeks. Blood samples were collected for the detection of serum alanine aminotransferase (ALT) , aspartate transaminase (AST) , triglycercide (TG) , total cholesterol (TC) and tumor necrosis factor alpha (TNF-α). The histological changes were observed under light microscope. Liver tissues were obtained for detection of malondisldehyde (MDA) contents and superoxidedismutase (SOD) activity. Results Compared with control group, the levels of ALT, AST, TG, TC, TNF-α and MDA increased (P < 0.05 ), but SOD decreased significantly ( P < O. 05 ) in model group. The severity degree of hepatic fatty degeneration aggravated and inflammation score significantly increased in model group. Compared with model group, all markers improved in cimetidine treatment group and cimetidine prevention group ( P < 0.05 ). The level of AST in cimetidine prevention group decreased significantly than that in the cimetidine treatment group ( P < O. 05 ). Conclusion Cimetidine can treat NASH rats induced by high-fat diet. It can prevent oxidative stress caused by free radical effectively, keep the balance of oxidation and anti-oxidation, improve the fatty degeneration of NASH rats, and alleviate the inflammatory reaction. So the early therapy is better for NASH.