阿托伐他汀对心室重塑和心肌AVP、TGF-β1的影响  

Effect of Atorvastatin on Ventricular Remodeling and Expression of Cardiac AVP and TGF-β1

作　　者：翟原生[1] 李杰[2] 卢贵华[2] 李庆朗 谢冬梅[2] 张菊红 梅卫义[1] 高修仁[2] ZHAI Yuan-sheng;LI Jie;LU Gui-hua;LI Qing-lang;XIE Dong-mei;ZHANG Ju-hong;MEI Wei-yi;GAO Xiu-ren(Department of Cardiology,The Eastern Section of the First Affiliated Hospital,NHC Key Laboratory of Assisted Circulation,Sun Yat-sen University,Guangzhou 510080,China;Department of Cardiology,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,China)

机构地区：[1]中山大学附属第一医院东院心血管内科/国家卫生健康委员会辅助循环重点实验室,广东广州510080 [2]中山大学附属第一医院心血管内科,广东广州510080

出　　处：《中山大学学报（医学科学版）》2020年第3期436-444,共9页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省自然科学基金(2015A030313011)。

摘　　要：【目的】探讨阿托伐他汀能否通过抑制AVP的分泌而延缓心肌纤维化,为改善心肌梗死后心室重塑提供新思路。【方法】通过结扎大鼠冠状动脉前降支建立大鼠心肌梗死模型。建模成功后将大鼠分为假手术组(sham组)、心肌梗死大鼠安慰剂治疗组(MI组)及心肌梗死大鼠阿托伐他汀治疗组(A组),每组各有10只大鼠。干预5周后,超声心动图检测大鼠心功能;处死大鼠后,收集心肌组织标本,计算左心室质量指数;ELISA法检测左心室非梗死区和血清的血管加压素(AVP)含量;Masson染色检测心肌间质纤维化水平;免疫组织化学染色检测左心室非梗死区Ⅰ型胶原的表达;Western blot测定左心室非梗死区转化生长因子-β1(TGF-β1)蛋白的表达。【结果】干预5周后,Sham组、MI组和A组分别存活10只、9只和10只大鼠。与Sham组大鼠比较,MI组和A组大鼠的左室质量(LVM)和左室质量指数(LVMI)增加、左室射血分数(LVEF)降低、心肌间质纤维化明显加重、左心室非梗死区Ⅰ型胶原蛋白的表达、AVP含量以及TGF-β1蛋白表达水平明显升高(P<0.05);阿托伐他汀干预后,LVM和LVMI降低、LVEF升高、心肌间质纤维化减轻、左心室非梗死区Ⅰ型胶原蛋白的表达、AVP的含量以及TGF-β1的蛋白表达水平显著降低(P<0.05)。【结论】阿托伐他汀能够改善心肌梗死后心室重塑,可能与抑制心室AVP的分泌及下调TGF-β1的表达有关。【Objective】To investigate the mechanism of atorvastatin improving ventricular remodeling in rats with myocardial infarction.【Methods】Ligation of left anterior descending coronary artery was performed to establish rat model of myocardial infarction.Thirty rats were divided into sham group(n=10),myocardial infarction group(n=10)and atorvastatin group(n=10).Echocardiography was used to examine cardiac function and left ventricular mass index(LVMI)was calculated.The content of arginine vasopressin(AVP)in left ventricular non-infarct area and serum was measured by ELISA.Masson staining was used to observed interstitial fibrosis of myocardium.Immunohistochemistry was used to measure the expression of typeⅠcollagen.The protein expression of transforming growth factor-β1(TGF-β1)was detected by western blot.【Results】After 5 weeks,the number of rats in sham group,myocardial infarction group and atorvastatin group was 10,9 and 10,respectively.Compared with sham group,LVEF was significantly decreased and,LVMI,inter?stitial fibrosis,the content of AVP,the expression of typeⅠcollagen and TGF-β1 in the left ventricular non-infarct area were significantly increased in myocardial infarction group and atorvastatin group(P<0.05).Atorvastatin significantly increased LVEF and decreased interstitial fibrosis,the content of AVP,the expression of typeⅠcollagen and TGF-β1 in the left ventricular non-infarct area(P<0.05).【Conclusion】Atorvastatin could ameliorate ventricular remodeling in rats with myocardial infarction,which might be associated with inhibiting the expression of AVP and TGF-β1.

关 键 词：血管加压素 阿托伐他汀 心室重塑 TGF-Β1 

分 类 号：R541[医药卫生—心血管疾病]