水飞蓟宾和卡托普利联合用药对大鼠酒精性肝病作用及机制的研究

摘要

目的 观察水飞蓟宾和卡托普利联合用药对酒精性肝病作用及其机制.方法 取健康的雄性SD 大鼠60 只,随机选取12 只作为正常组,其余48 只大鼠作为造模组,造模组采用35％、40％、45％、50％ 的酒精每周递增法分两次灌胃.造模6 周,病检有脂肪肝形成,将造模组随机分为4组:模型组、卡托普利组、水飞蓟宾、卡托普利和水飞蓟宾联合用药组,每组12 只,于两次灌胃酒精的间隙给药.连续给药6 周后,腹主动脉取血,制备肝匀浆、肝脏病理切片.检测大鼠血浆中天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),肝匀浆中核转录因子-κB(NF-κB)、肿瘤坏死因子-α(TNF-α) 水平.结果 模型组AST、ALT、LDL-C、 NF-κB 、TNF-α 均显著升高,HDL-C 降低(P < 0. 05);卡托普利和水飞蓟宾联合用药能降低大鼠血浆中ALT、AST、LDLC、NF-κB、TNF-α 的含量(P < 0. 05),升高血浆中HDL-C 的含量(P < 0. 05);肝切片检查显示,正常组大鼠肝细胞形态正常,肝血窦及门管区清晰,模型组大鼠肝细胞肿大,排列散乱伴有炎细胞浸润,大部分肝细胞发生脂肪变性,联合用药组只有少量肝细胞发生脂肪变性,且大多数肝细胞排列比较正常,细胞水肿较少,炎细胞浸润较低.结论 卡托普利和水飞蓟宾联合用药对酒精型肝病大鼠有显著的治疗作用,其机制可能与降低NF-κB、TNF-α 的水平有关.%Objective To observe the effect of combined use of silybin and captopril on alcohol-induced liver disease and its mechanism. Methods A total of 60 healthy male SD rats were randomly selected as the normal group and the remaining 48 rats were used as the modeling group. The model was made up of 35％,40％,45％,50％ alcohol by weekly increment method. The method was administered twice. 6 weeks of modeling,pathological examination showed fatty liver formation. The model group was randomly divided into 4 groups: model group,captopril group,silymarin,captopril and silybin combined groups,12 in each group,In the gap between two intragastric administrations. Six weeks after continuous administration,blood was collected from the abdominal aorta to prepare liver homogenate and liver pathological sections. Aspartate aminotransferase (AST),alanine aminotransferase (ALT),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C),nuclear factor-κB (NF-κB),tumor necrosis factor-α (TNF-α) were detected. Results The AST,ALT,LDL-C,NF-κB, TNF-α in the model group were all significantly increased,HDL-C was significantly decreased(P < 0. 05); captopril and silybin combined use reduced plasma ALT,AST,and LDL-C NF-κB,and TNF-α levels(P < 0. 05) and increased plasma HDL-C levels(P < 0. 05). The biopsy showed normal morphology of the liver cells in the normal group,and the hepatic sinusoids and portal area were clear. The hepatocytes in the model group were swollen,and the arrangement was scattered with inflammatory cell infiltration. Most of the hepatocytes developed fatty degeneration, and only a small number of hepatocytes in the combination group developed steatosis,and most of the hepatocytes were arranged normally,with less cell edema and lower inflammatory cell infiltration. Conclusion Captopril combined with silybin has a significant therapeutic effect on rats with alcoholic liver disease,and its mechanism may be related to the decrease of NF-κB and TNF-α levels.