美他多辛对酒精性脂肪肝大鼠CYP2E1表达的影响及其预防作用  

Effects of metadoxine on CYP2E1 expression and preventive role in rats with alcoholinduced fatty liver

作　　者：王宇[1] 苏乐群[2] 王文奇[2] 张卫强[1] 

机构地区：[1]山东大学药学院,山东济南250012 [2]山东大学附属千佛山医院,山东济南250014

出　　处：《中国新药与临床杂志》2011年第2期131-135,共5页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的探讨美他多辛对酒精性脂肪肝大鼠肝组织中CYP2E1表达的影响及其治疗酒精性脂肪肝的机制。方法 30只清洁级Wistar大鼠随机分为3组:正常组、模型组和预防组。采用乙醇(8g·kg^(-1)·d^(-1))灌胃,每日2次,间隔8h,持续8wk,建立酒精性脂肪肝动物模型。正常组:不灌服乙醇,给予等体积生理盐水;模型组:在每次灌服乙醇1h后,给予等体积灭菌注射用水;预防组:在每次灌服乙醇1h后给予美他多辛(300mg·kg^(-1)·d^(-1))。8 wk灌胃结束后,B超、HE染色和油红O染色观察脂肪肝形态变化,采用自动生化仪检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、三酰甘油(TG)、总胆固醇(TC)含量,免疫组化和蛋白印迹法检测大鼠肝组织中CYP2E1的表达。结果模型组ALT、AST、TG、TC含量明显升高,与正常组和预防组比较有显著差异(P<0.01,P<0.05),预防组明显降低CYP2E1表达与模型组比较有显著差异(P<0.01)。结论美他多辛通过抑制CYP2E1表达的上调,有效预防酒精性脂肪肝的发展。AIM To investigate the effects of metadoxine on CYP2E1 expression in liver tissue and determine the role of metadoxine in rats with alcohol-induced fatty liver. METHODS Thirty clean Wistar rats were randomized into nomal group, model group and prevention group. The alcoholic fatty liver model was induced by alcohol （8 g·kg^-1·d^-1, ig, twice daily for 8 wk）. The rats in normal group were daily given the same volume of normal saline. The rats in model group were given sterile water 1 h after intragastric alcohol infusion. The rats in prevention group were given metadoxine （300 mg·kg^-1·d^-1） 1 h after intragastrie alcohol infusion. To detect the morphological changes, 8 wk after intragastric alcohol infusion, the liver tissues were observed by ultrasonography, HE-staining and Oil Red O stainning. The level of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, triglyceride （TG） and total cholesterol （TC） in serum were detected by automatic biochemical analyzer, and the expression of CYP2E1 in liver tissue was detected by immunohistochemistry and Western blot. RESULTS The level of ALT, AST and TG in model group were significantly higher than normal group and prevention group （P 〈 0.01, P 〈 0.05）. The expression of CYP2E1 in prevention group was remarkably lower than model group （P 〈 0.01 ）. CONCLUSION Metadoxine is effective in preventing the development of alcoholic fatty liver by down-regulating the expression of CYP2E1.

关 键 词：美他多辛 CYP2E1 脂肪肝 酒精 化学预防 大鼠 

分 类 号：R965[医药卫生—药理学] R975[医药卫生—药学]