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内皮素受体阻断剂在高血压糖尿病鼠中的肾脏保护作用及其可能机制 被引量:6

Renoprotective effect of endothelin receptor antagonist bosentan and its possible mechanism
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摘要 目的 探讨核因子kB(NF-kB)和周期素激酶抑制剂(CKI)p21、p27在糖尿病高血压进展中的可能机制及非选择性内皮素受体阻断剂波生坦(bosentan)的干预作用。方法 自发性高血压大鼠经链脲佐菌素诱导成的糖尿病模型(SHR-DM),设非选择性内皮素受体阻断剂波生坦(bosentan)+长效钙离子拮抗剂氨氯地平(amlodipine)组、amlodipine组、血管紧张素转换酶抑制剂西拉普利(cilazapril)组和非治疗组,4周后用免疫组织化学方法和Western blot方法观察肾脏NF-kB、p21、p27与转化生长因子(TGF-β1)的变化。结果 bosentan可以明显抑制SHR-DM组肾脏NF-kB、TGF-β1、p21和p27的表达,其肾脏保护作用与cilazapril相似。结论bosentan的肾脏保护作用可能与干预NF-kB-TGF-β1-p21、p27通路有关。 Objective To investigate the possible mechanism of nuclear factor-KB, cyclin kinase inhibitor p21 ,p27 in diabetic hypertensive nephropathy and the interference action of bosentan. Methods Streptozotocin-induced diabetic SHR were divided into bosentan + amlodipine group, amlodipine group, cilazapril group and untreated group. Changes of nuclear factor-KB(NF-KB), p21, p27 and transforming growth factor (TGF) B1 were determined by immunohislochemistry and Western blot at 4th week. Results Bosentan inhibited obviously the expression of NF-KB, p21, p27 and TGF-Bl in diabetic hypertensive group, which exhibited same renoprotective effect as did cilazapril. Conclusion The renoprotective effect of bosentan may be related with its interference in the pathway of NF-KB-TGF-B1-p21 ,p27.
出处 《中华肾脏病杂志》 CAS CSCD 北大核心 2002年第2期107-110,共4页 Chinese Journal of Nephrology
基金 上海市卫生系统百人计划资助项目(98BR038)
关键词 糖尿病 高血压 内皮素受体阻断剂 核因子-κB 周期素激酶抑制剂 Diabetes mellitus Hypertension Endothelin receptor antagonist Nuclear factor-KB Cyclin kinase inhibitor
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  • 1Liu J J,J Hypertens,1993年,11卷,977页

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