替米沙坦对阿霉素肾损伤大鼠血浆中血管紧张素(1~7)水平的影响

目的 观察替米沙坦对阿霉素(adriamycin, ADR)诱导的肾损伤大鼠血浆中血管紧张素(1~7)[Ang(1~7)]水平的影响.方法 50只健康、雄性SD大鼠,随机分为对照组(n=10)、ADR模型组(n=20)、替米沙坦组(n=20).对照组腹腔注射同等剂量的生理盐水;另两组均腹腔注射ADR 2.5mg/kg,每周3次,共2周,累积量15mg/kg,同时替米沙坦组给予替米沙坦10mg/(kg·d)(累积量420mg/kg)灌胃干预共6周.实验过程中观察大鼠精神、活动、饮食等一般情况.于末次注射停药后4周,检测大鼠终末体重、血浆Ang(1~7)水平,处死大鼠后制作肾脏病理切片并观察组织学变化.结果 ADR模型组及替米沙坦组大鼠体重均较对照组下降(P均<0.01),但替米沙坦组体重较ADR模型组有所增加(P<0.01),ADR模型组与替米沙坦组大鼠血浆Ang(1~7)的水平较对照组亦下降(4.27±2.79 vs 10.26±2.39ng/ml, P<0.01;7.16±2.13 vs 10.26±2.39ng/ml,P<0.05),但替米沙坦组血浆Ang(1~7)水平较ADR模型组升高(P<0.05),组织病理学变化:与对照组相比,ADR模型组大鼠肾脏炎性细胞成簇聚集、浸润明显增多,且肾小管上皮细胞水肿;替米沙坦组炎性细胞浸润则较模型组明显减少,肾小管上皮细胞水肿程度亦减轻.结论 替米沙坦能够提高阿霉素肾损伤大鼠血浆中Ang(1~7)的水平,且该变化水平可能与肾脏炎性反应的严重程度有一定的相关性.

Effects of Telmisartan on the Plasma Angiotensin-(1-7) Levels in Adriamycin Induced Renal Injury in Rats.

Objective To investigate effects of Telmisartan on plasma angiotensin(1-7) [Ang(1-7)] levels in Adriamycin (ADR)-induced renal injury in rats. Method Male Sprague-Dawley rats were randomly divided into controls (n=10), ADR-model group (n=20) and Telmisartan group (n=20). Control rats were intraperitoneally injected the same volume of normal saline, and the other two groups were all intraperitoneally injected a cumulative dose of 15 mg/kg of ADR (each dose of 2.5mg/kg×6) for 2 weeks, and Telmisartan group was simultaneously treated with Telmisartan (10mg/kg daily, total 420mg/kg) orally for 6 weeks. During the test, rats were observed for spirit, activity, diet and other general living conditions. Four weeks after drug withdrawal, terminal weight of rats were detected by scale, plasma Ang (1-7) levels was detected by ELISA, and the histological changes of renal were observed by HE staining. Results The weight of rats in ADR-model group and Telmisartan group were both decreased (P<0.01), but in Telmisartan group, rats weight were increased than in ADR-model group (P<0.01), plasma Ang (1-7) levels in both of ADR-model group and Telmisartan group were also decreased (4.27±2.79 vs 10.26±2.39ng/ml, P<0.01; 7.16±2.13 vs 10.26±2.39ng/ml, P<0.05). However, in Telmisartan group, it was higher than in ADR-model group (P<0.05). Histological changes of rat kidney indicated that inflammatory cells were clustered and increased significantly, and the renal tubular epithelial cells edema in model group. In Telmisartan group, inflammatory cells were obviously reduced and the degree of dropsy in renal tubular epithelial cells were also alleviated. Conclusion Plasma Ang (1-7) levels were improved in ADR-induced renal injury in rats after the intervention of Telmisartan, and there may be some correlation between the plasma Ang (1-7) levels and the severity of inflammation in Kidney.