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直接肾素抑制剂阿利吉仑在预防大鼠实验性对比剂肾病中的作用。

Effect of the direct renin inhibitor aliskiren in the prevention of experimental contrast-induced nephropathy in the rat.

机构信息

Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey.

出版信息

Kidney Blood Press Res. 2012;35(6):425-30. doi: 10.1159/000336104. Epub 2012 Jun 6.

Abstract

BACKGROUND

Renal vasoconstriction, activated by the renin-angiotensin system, plays a pivotal role in the pathogenesis of contrast-induced nephropathy (CIN). The purpose of this study was to evaluate the effect of aliskiren, a direct renin inhibitor, for the prophylaxis of experimental CIN in the rat.

METHODS

Thirty-two Wistar albino rats were divided into four groups of 8 rats each, namely the control (C), aliskiren (A), contrast media (CM) and aliskiren plus contrast media (ACM) groups. Aliskiren was given orally at a dose of 50 mg/kg/day once daily for 5 consecutive days. CIN was induced by intravenous administration of indomethacin, N-nitro-L-arginine methyl ester and high-osmolar contrast medium meglumine amidotrizoate. Renal function parameters, kidney histology and tubular expression of vascular endothelial growth factor were determined.

RESULTS

Mean serum creatinine was significantly lower (p < 0.001) and mean creatinine clearance was higher (p < 0.001) in the ACM group compared with the CM group. However, there were no differences between the ACM and CM groups in terms of tubular necrosis, proteinaceous casts, medullary congestion and vascular endothelial growth factor expression.

CONCLUSION

Our preliminary data seem to suggest a potential role of aliskiren for the prophylaxis of CIN in an experimental rat model.

摘要

背景

肾血管收缩,由肾素-血管紧张素系统激活,在造影剂肾病(CIN)的发病机制中起着关键作用。本研究的目的是评估直接肾素抑制剂阿利克仑预防实验性大鼠 CIN 的效果。

方法

32 只 Wistar 白化大鼠随机分为 4 组,每组 8 只,分别为对照组(C)、阿利克仑组(A)、造影剂组(CM)和阿利克仑加造影剂组(ACM)。阿利克仑以 50mg/kg/天的剂量口服,每天一次,连续 5 天。CIN 通过静脉注射吲哚美辛、N-硝基-L-精氨酸甲酯和高渗造影剂 amidotrizoate 诱导。测定肾功能参数、肾脏组织学和血管内皮生长因子的管状表达。

结果

与 CM 组相比,ACM 组的平均血清肌酐明显降低(p < 0.001),肌酐清除率明显升高(p < 0.001)。然而,ACM 组和 CM 组之间在肾小管坏死、蛋白样铸型、髓质充血和血管内皮生长因子表达方面没有差异。

结论

我们的初步数据似乎表明阿利克仑在实验性大鼠模型中对 CIN 的预防具有潜在作用。

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