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替米沙坦与吡格列酮对糖尿病大鼠缺血/再灌注诱导肾损伤的肾保护作用。

Renoprotective activity of telmisartan versus pioglitazone on ischemia/reperfusion induced renal damage in diabetic rats.

机构信息

Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.

出版信息

Eur Rev Med Pharmacol Sci. 2012 May;16(5):600-9.

PMID:22774400
Abstract

OBJECTIVES

Diabetes mellitus (DM) causes organ dysfunction and increases the sensitivity of organs to damages.To test this hypothesis, we used renal ischemia/reperfusion (I/R) experiment to evaluate the renoprotective activity of telmisartan versus pioglitazone on I/R induced renal damage in diabetic rats.

MATERIALS AND METHODS

Renal I/R was performed in both normal and diabetic rats. The protocol comprised ischemia for 45 minutes followed by the reperfusion for 24 hours and a treatment period of two weeks before induction of ischemia.

RESULTS

Renal I/R in both control and diabetic rats induced marked renal dysfunction associated with a significant increase in the arterial pressure, tumor necrosis factor alpha (TNF-alpha) levels, and the malondialdehyde formation (MDA). The activities of the anti-oxidant enzymes such as reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were found to be decreased significantly compared to control rats. Diabetic animals that underwent renal I/R exhibited a significant increase in all the studied parameters with a reduction in the anti-oxidant enzymes as compared to non-diabetic rats. Histo-pathological studies confirm these results. Treatment with pioglitazone or telmisartan demonstrated a significant improvement in the reperfusion-induced renal injury in comparison with diabetic I/R group, without difference between the two treated groups. Therefore, the treatment with pioglitazone or telmisartan have the same corrective effect.

CONCLUSIONS

Type 2 diabetes had exaggerated renal I/R injury in STZ-NAD induced diabetes. Telmisartan treatment is equieffective as pioglitazone in attenuating acute I/R-induced renal injury in diabetic rats by a modification in the oxidative stress and the inflammation.

摘要

目的

糖尿病(DM)会导致器官功能障碍,并增加器官对损伤的敏感性。为了验证这一假说,我们使用肾缺血/再灌注(I/R)实验来评估替米沙坦与吡格列酮对糖尿病大鼠 I/R 诱导的肾损伤的肾保护作用。

材料与方法

在正常和糖尿病大鼠中进行肾 I/R。方案包括缺血 45 分钟,然后再灌注 24 小时,并在诱导缺血前进行两周的治疗期。

结果

在对照和糖尿病大鼠中,肾 I/R 均导致明显的肾功能障碍,同时动脉压、肿瘤坏死因子-α(TNF-α)水平和丙二醛形成(MDA)显著增加。与对照大鼠相比,抗氧化酶如还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的活性明显降低。接受肾 I/R 的糖尿病动物与非糖尿病大鼠相比,所有研究参数均显著增加,抗氧化酶减少。组织病理学研究证实了这些结果。与糖尿病 I/R 组相比,吡格列酮或替米沙坦治疗显著改善了再灌注引起的肾损伤,而两种治疗组之间没有差异。因此,吡格列酮或替米沙坦的治疗具有相同的矫正效果。

结论

STZ-NAD 诱导的 2 型糖尿病使肾 I/R 损伤加重。替米沙坦治疗通过减轻氧化应激和炎症,对糖尿病大鼠急性 I/R 诱导的肾损伤具有与吡格列酮相同的缓解作用。

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