氯沙坦及A779对糖尿病心肌病大鼠心肌间质纤维化的影响  

Effect of Losartan and A779 on myocardial interstitial fibrosis in diabetic cardiomyopathy

作　　者：胡圣[1] 张绪洪[1] 董波[1] 朱梅[2] 张月辉[1] 于庆涛[3] 

机构地区：[1]山东大学附属省立医院心内科,济南250021 [2]山东大学附属省立医院B超室,济南250021 [3]山东大学附属省立医院内分泌科,济南250021

出　　处：《山东大学学报（医学版）》2008年第4期362-365,共4页Journal of Shandong University:Health Sciences

摘　　要：目的观察氯沙坦对糖尿病心肌病大鼠心肌间质纤维化的影响并探讨其机制。方法将39只雄性Wistar大鼠给予链脲佐菌素(STZ)55 mg/kg一次性腹腔注射12周后,将血糖>16.7 mol/L且具有多饮、多食、多尿现象的36只大鼠纳入实验。实验大鼠随机分为糖尿病心肌病(DCM)组、氯沙坦组和A779+氯沙坦组,每组12只。给予氯沙坦组大鼠氯沙坦10 mg/(kg.d)灌胃,给予A779+氯沙坦组大鼠氯沙坦10 mg/(kg.d)灌胃和血管紧张素-(1-7)受体拮抗剂A779 100 ng/(kg.d)尾静脉注射,给予DCM组大鼠等量生理盐水灌胃,治疗持续4周。第16周末采用心脏超声、Masson染色及RT-PCR的方法测定大鼠的左室舒张末期内径(LVIDd)、左室收缩末期内径(LVIDs)、短轴缩短率(FS)、左室射血分数(LVEF)、E/A(E峰/A峰)、左室心肌胶原含量、ACE2 mRNA的表达。结果与DCM组比较,氯沙坦组和A779+氯沙坦组大鼠的LVIDs、LVIDd降低(P<0.01),E/A、FS、LVEF升高(P<0.01),左室胶原含量减轻(P<0.01),ACE2 mRNA表达增高(P<0.01);与氯沙坦组比较,A779+氯沙坦组大鼠LVIDs、LVIDd升高(P<0.05),E/A、FS、LVEF降低(P<0.05),左室胶原含量升高(P<0.05),ACE2 mRNA表达无明显差异。结论氯沙坦通过Ang-(1-7)途径减少纤维化及改善心功能。Objective To investigate the effect of Losartan and A779 on myocardial interstitial fibrosis in diabetic cardiomyopathy （1）CM）. Methods Thirty-nine male Wistar rats were intraperitoneally injected with streptozocin （SVZ） to induce hyperglycemia. After 12 weeks of the SYZ injection, rats whose blood glucose was higher than 16.7 mmol/L and who had polydipsia, hyperphagia and polyuria were randomly divided into 3 groups： the DCM group, the Losartan group and the A779 ＋ Losartan group. The DCM group was subjected to peafusion of normal sahne into the stomach once daily, the Losartan group perfusion of Losartan once daily, and the A779 ＋ Losartan group perfusion of Losartan and injection of A779 through the tail vein once daily. At the end of the experiment, LVIDs, LVIDd, E/A, LVEF and FS were determined by ultrasound. Then the collagen level was deterand the mRNA expression of the angiotensin-conversion enzyme 2 （ACE2） was determined by realtime RT-PCR. Results By the end of the experiment, the LVIDs, LVIDd and the collagen level of the Losartan group and the A779 ＋ Losartan group were lower than those of the DCM group （ P 〈 0.01 ）, also the E/A, FS, LVEF levels and the expression of ACE2 mRNA of the Losartan group and the A779 ＋ Losartan group were higher than those of the DCM group（ P 〈 0.01 ）. The LVIDs, LVIDd and collagen content of the A779 ＋ Losartan group were higher than those of the Losartan group（ P 〈 0.05）, and E/A, FS and LVEF of the A779 ＋ Losartan group were lower than those of the Losartan group（ P 〈 0.05）. However the expression of ACE2 mRNA had no difference between the Losartan group and the A779 ＋ Losartan group. Conclusions Losartan ameliorates the myocardial mterstitial fibrosis via Ang-（1-7）.

关 键 词：氯沙坦 血管紧张素-(1-7) 血管紧张素转换酶-2 A779 糖尿病 心肌病 大鼠 WISTAR 

分 类 号：R542.2[医药卫生—心血管疾病] R-332[医药卫生—内科学]