甲氰咪胍对非酒精性脂肪性肝炎大鼠脂质过氧化作用的影响

Influence of cimetidine on lipid peroxidation in rats with nonalcoholic steatohepatitis

目的:探讨甲氰咪胍对非酒精性脂肪性肝炎(NASH)大鼠脂质过氧化作用的影响。方法:雄性SD大鼠30只,随机分为3组,正常对照组、模型组、甲氰咪胍组,正常组普通饲料喂养,模型组喂高脂饮食,甲氰咪胍组在高脂饮食12 w后给予甲氰咪胍灌胃治疗。16 w末处死各组大鼠,测定血清转氨酶(ALT、AST)、血脂(TC、TG)、肝匀浆丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性,同时测定细胞色素P450(CYP450)和细胞色素2E1(CYP2E1)含量,光镜下观察肝组织学改变。结果:与正常组比较,模型组大鼠血清TG、TC水平,肝组织脂质过氧化产物MDA含量明显增高,而抗氧化物SOD活性明显降低,肝脏的脂肪变性程度和炎症活动度均显著增高,细胞色素P450和CYP2E1含量显著增高。甲氰咪胍组各项指标较模型组有明显改善(P<0.05)。结论:甲氰咪胍通过抑制CYP2E1表达与其密切相关的脂质过氧化作用,改善NASH大鼠脂肪变性,减轻炎症反应。

Objective： To investigate effects of cimetidine on lipid peroxidation in rats with nonalcoholic steatohepatitis （NASH）. Methods： 30 male SD rats were randomly divided into the control group（ordinary diet）, model group（high- fat diet）, cimetidine treated group（intragastric administration with cimetidine after feeding high - fat diet 12 weeks）. The rats in each group were killed at the end of 16 w. Blood samples were collected for the detection of serum alanine aminotransferase （ALT）, aspartate transaminase （AST）, total cholesterol （TC） and triglyeride （TG）. Liver tissues were obtained for detection of the contents of malondialdehyde （MDA）, eytochrome P450 and CYP2E1 as well as superoxide dismutase （SOD） activity. The histological changes were observed under light microscope. Results： In the model group the levels of TG and TC in serum, the contents of MDA, cytochrome P450 and CYP2E1 in liver tissue increased significantly compared with those in the control group except anti - oxide SOD which decreased significantly. The severity degree of hepatic fatty degeneration was more aggravated and inflammation score was significantly higher in the model group than those in normal rats. However, the markers such as MDA, SOD, CYP450, CYP2E1 and etc. were all markedly improved in cimetidine treated group. Conclusion：Cimetidine can improve fatty degeneration and reduce inflammation of NASH rat by inhibiting CYP2E1 expression which is closely related to lipid peroxidation.