福辛普利对非酒精性脂肪性肝炎大鼠肝组织ACE和ACE2基因mRNA转录水平的影响  

Effect of fosinopril on transcription levels of angiotensin-converting enzyme and angiotensinconverting enzyme 2 mRNAs in liver tissues of rats with nonalcoholic steatohepatitis

作　　者：刘波[1] 吴小翎[1] 张霞[1] 张伟[1] 吴蓉[1] 肖晓秋[2] 张凤[1] 周华梅[1] 王璐璐[1] 

机构地区：[1]重庆医科大学附属第二医院消化内科,重庆400010 [2]重庆医科大学生命科学研究院,重庆400016

出　　处：《中国生物制品学杂志》2012年第12期1658-1662,共5页Chinese Journal of Biologicals

摘　　要：目的探讨福辛普利对高脂饮食诱导的非酒精性脂肪性肝炎(Nonalcoholic steatohepatitis,NASH)大鼠肝组织ACE和ACE2基因mRNA转录水平的影响,为阐明NASH的发病机制及探索新的治疗策略提供实验依据。方法将40只雄性SD大鼠用普通饲料喂养1周后,随机分为4组:正常对照组(NC组,普通饲料+生理盐水1 ml灌胃)、高脂组(HC组,高脂饲料+生理盐水1 ml灌胃)、药物对照组[NF组,正常饲料+福辛普利3.6 mg/(kg.d)灌胃]和药物干预组[HF组,高脂饲料+福辛普利3.6 mg/(kg.d)灌胃],每组10只。给药24周后,分析各组大鼠肝组织病理学变化,检测各组大鼠血清中谷丙转氨酶(Alanine aminotransferase,ALT)、碱性磷酸酶(Alkaline phosphatase,ALP)、甘油三酯(Triglycerides,TG)、低密度脂蛋白(Low-density lipoprotein,LDL)、转化生长因子-β(Transforming growth factor-β,TGF-β)、血管紧张素转换酶(Angiotensin-convert ingenzyme,ACE)、ACE2、血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)和Ang(-1-7)的水平;RT-PCR检测各组大鼠肝组织ACE和ACE2基因mRNA的转录水平;Western blot检测各组大鼠肝组织Ⅰ型胶原蛋白(CollagenⅠ)的表达水平。结果给药24周后,HF组非酒精脂肪性肝病活动度评分和肝纤维化程度与HC组相比,均明显下降(P<0.001);HF组血清中ALT、ALP、TG、LDL、TGF-β、ACE和AngⅡ的水平均明显低于HC组(P<0.05),而ACE2和Ang(-1-7)的水平均明显高于HC组(P<0.05);福辛普利可显著降低肝组织ACE基因mRNA的转录水平(P<0.001)和CollagenⅠ蛋白的表达水平(P<0.01),升高ACE2基因mRNA的转录水平(P<0.01)。结论福辛普利可能通过下调ACE和上调ACE2的生成和表达,从而降低AngⅡ和升高Ang(-1-7)的生成,具有改善NASH和抗肝纤维化作用。本实验为阐明NASH的发病机制及探索新的治疗策略提供了实验依据。Objective To investigate the effect of fosinopril on transcription levels of mRNAs of angiotensin-converting enzyme（ACE）and ACE2 in liver tissue of rats with nonalcoholic steatohepatitis（NASH）induced by high lipid diet.Methods A total of 40 male SD rats were fed with normal forage for 1 week and randomly divided into four groups,10 for each.The rats in normal control（NC）group were fed with normal forage and administered with 1 ml of physiological saline by gavage,while those in high lipid（HC）group were fed with high lipid forage and administered with 1 ml of physiological saline by gavage,those in drug control（NF） group were fed with normal forage and administered with 3.6 mg /（kg·d）fosinopril by gavage,and those in drug intervention（HF） group were fed with high lipid forage and administered with 3.6 mg /（kg·d）fosinopril by gavage.Twenty-four hours after treatment,the rats in various groups were observed for pathological change in liver tissue,and determined for alanine aminotransferase（ALT）,alkaline phosphatase（ALP）,triglycerides（TG）,low-density lipoprotein（LDL）,transforming growth factor-β（TGF-β）,angiotensinconverting enzyme（ACE）,ACE2,angiotensin Ⅱ（Ang Ⅱ）and Ang-（1-7）levels in sera.The transcription levels of ACE and ACE2 mRNAs in liver tissues of rats in various groups were determined by RT-PCR,while the expression level of collagen Ⅰ by Western blot.Results As compared with those in HC group,the score for activity of NASH and degree of fibrosis of rats in HF group 24 h after treatment decreased significantly（P 0.001）,and the serum ALT,ALP,TG,LDL,TGF-β,ACE and Ang II levels decreased significantly（P 0.05）,while the ACE2 and Ang-（1-7）levels increased significantly（P 0.05）.Fosinopril decreased the transcription level of ACE mRNA（P 0.001）and the expression level of collagen Ⅰ in liver tissue significantly（P 0.01）,while increased the transcription level of ACE2 mRNA（P 0.01）.Conclusion Fosinopril decreased the A

关 键 词：福辛普利 非酒精性脂肪性肝炎 肝纤维化 血管紧张素转换酶 血管紧张素Ⅱ 

分 类 号：R575.1[医药卫生—消化系统]