比较雷米普利与卡托普利对糖尿病大鼠心肌间质重构的影响

To Investigate the Protection of Captopril and Ramipril on the Interstitium of Diabetic Cardiomyopathy

目的:通过观察雷米普利与卡托普利对糖尿病大鼠心脏指数、心肌局部血管紧张素Ⅱ(AngⅡ)、Caspase-3蛋白阳性染色指数、心肌细胞凋亡指数(AI)的影响,探讨两者对糖尿病大鼠心肌病的可能保护机制。方法:40只健康雄性SD大鼠随机分为10只正常对照组和30只糖尿病组,糖尿病组用链脲佐菌素(STZ)注射建模,成功后随机分为糖尿病未治疗组(糖尿病对照组)、雷米普利治疗组和卡托普利治疗组,每组10只。治疗组按药品说明书的推荐以雷米普利2.5mg/(kg.d)水溶液灌胃,卡托普利50mg/(kg.d)水溶液灌胃,正常对照组和糖尿病对照组每天以同等体积生理盐水灌胃。给药9周后,麻醉处死动物,放射免疫法测定心肌局部AngⅡ的含量,ABC免疫组化法检测Caspase-3蛋白阳性染色指数,免疫组化法检测Ⅰ、Ⅲ型胶原的含量。结果:与正常对照组相比,糖尿病对照组与治疗组心脏指数均增大(P<0.05),AngⅡ含量显著升高(P<0.05),心肌细胞凋亡指数(AI)明显增高(P<0.05),Caspase-3蛋白阳性染色指数也增高(P<0.05);用雷米普利和卡托普利治疗后,上述指标均有显著改善,雷米普利组较卡托普利组心脏指数、Ⅰ、Ⅲ型胶原含量改善不明显(P<0.05),其余指标两组比较没有统计学差别(P>0.05)。结论:糖尿病心肌病中心肌间质有重构现象发生,雷米普利与卡托普利均可以通过降低AngⅡ、Caspase-3阳性蛋白指数来改善心脏的功能,而且两组相比稍有差别。

Objective. To study the possible protection mechanism through the effect of Captopril and Ramipril on the diabetic rats cardiac index, the expression of Ang Ⅱ , AI,Caspase-3. Methods： 36 male SD rats were randomly put in to 2 groups , 9 as normal control group and the other 27 as diabetic group which was induced by STZ, after the model was constructed successfully , again randomly devided in to diabetic control group, Captopril treatedgroup and ramipril treated group,each contains 9. Captopril was administra- l^ed at the dose of 50mg/kg once a day, Ramipril was administrated at the dose of 2. 5mg/kg once a day-while in the diabetic control group and the normal control the same volume sodium chloride was administrated, nine weeks later , all rats were executed in the condition of anaesthesia, Radioimmunity was used to measure the expression of Ang Ⅱ, ABC immunohistochemical staining was used respectively to detect the changes of apoptosis and protein expression of Caspase-3 , immunohistochemistry was used to measure expression levels of type Ⅰ collagen, type Ⅲ collagen. Results. Compared to the normal control , the cardiac index,the content of AngⅡ ,AI and the protein expression of Caspase-3 significantly increased （P〈0.05） ;after treated by Captopril and Ramipril, the above was all improved, but cardiac index was significantly higher in the Captopril treated group （P〈0. 05）,others were not different in two groups . Conclusion： The remodeling of Interstitium took place in the diabetic cardiomyopathy ,Captopril and ramipril could improve the function of heart by the means of decreasing the content of Ang Ⅱ , AI and protein expression of Caspase-3, there was less difference in the two groups.