佐芬普利对肾血管性高血压大鼠肾脏血管肾张素转换酶2及Mas受体的影响  

Influence of Zofenopril to renovascular hypertension rats on ACE2 and Mas with kidney

作　　者：秦晓毅[1] 卢新政[1] 张辉[1] 杨玉青[1] 郑宏健[1] 黄红娟[1] 侯麦花[1] 陈明龙[1] 孔祥清[1] 黄峻[1] 

机构地区：[1]南京医科大学第一附属医院心内科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2013年第6期749-753,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金面上项目(30770890)

摘　　要：目的:探讨佐芬普利对大鼠肾血管性高血压、心肌肥厚及肾脏血管紧张素转换酶2(ACE2)及血管紧张素1-7(Ang1-7)受体Mas的影响。方法:清洁型雄性SD大鼠70只,随机分为假手术组(S)20只、2K1C手术组50只。采用两肾一夹法(two-kidney one clip,2K1C)制作肾血管性高血压模型,高血压造模成功大鼠46只,随机分为2K1C+蒸馏水组(K)23只、2K1C+佐芬普利组(Z)23只。分别于术后第4、8、12周,无创血压仪套尾法监测血压,二维超声心动图监测心脏结构和功能;术后第8、12周分别处死大鼠取其代偿肾脏,荧光定量PCR检测其ACE2及Ang1-7受体Mas mRNA表达,Western blot技术检测ACE2及Mas蛋白表达。结果:①术后K组各时间段血压均明显升高,Z组较K组血压显著降低(P均<0.01);②术后第8、12周,K组收缩及舒张末期左室后壁厚度、室间隔厚度均显著增加,Z组上述指标明显改善(P均<0.01),第12周时K组射血分数显著降低,Z组显著增加(P均<0.01);③K组中,Mas基因及蛋白水平第8周时上调,第12周时下调,与K组相比,Z组第8周时明显下调,第12周时明显上调(P均<0.01);K组中ACE2基因及蛋白水平第8周时上调,第12周时无显著变化,与K组相比,Z组第8周时上调,第12周时显著下降(P<0.01);结论:2K1C法成功复制肾血管性高血压大鼠模型,并致高血压性心脏改变;佐芬普利不仅能显著降低肾性高血压大鼠血压,还能改善心肌重构,上调肾脏组织中Mas基因与蛋白水平,下调ACE2基因及蛋白水平。Objective：To discuss the effect of ACE2/angiotensin1-7/Mas receptor axis in renovascular hypertension rat kidney and myocardial hypertrophy of Zofenopril.Methods：Seventy male SD rats weighting 190～210 g were randomly divided into sham operation group（S,n=20） and 2 kidney 1 clip（2K1C） group（n=50）.There were 46 rats developed hypertension successfully,and they were randomly divided into 2K1C ＋ distilled water group（K,n=23） and 2K1C＋Zofenopril group（Z,n=23）.The systolic blood pressure were measured（SBP） by tail artery sleeve method at the end of 4th,8th and 12th week respectively and ultrasonography was taken at the same time.After that,collected the right kidney at the 8th and 12th week respectively,detected the mRNA levels of ACE2 and Mas by RT-PCR,tested the protein expressions of ACE2 and Mas receptor by Western blot.Results：①Compared with the S group,the blood pressure of K group increased remarkablely（P〈0.01） at the end of the 4th,8th and 12th week respectively,and decreased significantly（P〈0.01） after been treated with Zofenoprilat.②The end-diastolic and end-systolic ventricular septal thickness,left ventricular wall thickness in K group were significantly enhanced compared with S group at the end of the 8th and 12th week respectively（P〈0.01）,EF reduced significantly at the 12th week.The front index were decreased（P〈0.01,respectively） and EF enhanced remarkably after been treated with Zofenopril.③ The mRNA and protein expression of Mas receptor were up-regulated at the 8th week,while down-regulation occurred at the 12th week in K group contrast to S group.After being treated with Zofenopril,they decreased at the 8th week and elevated at the 12th week（P〈0.01,respectively）.The mRNA and protein expression of ACE2 were higher in K group in the two periods（P〈0.01,respectively） compared to S group.When treated with Zofenopril,it was reduced remarkably（P〈0.01）.Conclusion：We estabished renovascular hypertension model successfully by

关 键 词：佐芬普利 肾血管性高血压 肾脏 血管紧张素转换酶2 MAS受体 

分 类 号：R541.3[医药卫生—心血管疾病]