摘要
目的 探讨缬沙坦对自发性高血压大鼠(SHR)肾结构与功能的保护作用及其机制。方法将 20只 SHH随机分为 3组,治疗组分别以苯那普利( 10 mg· kg-1· d-1)和缬沙坦( 10 mg· kg-1·d-1)灌胃 12周,观察大鼠的血压、尿蛋白、血和尿一氧化氮( NO )水平及肾组织病理改变;并用逆转录-聚合酶链反应(RT-PCR)方法测定肾皮质转化生长因子β1(TGF-β1)mRNA表达。结果缬沙坦和苯那普利治疗组的尿蛋白显著减少(P<0.01),且缬沙坦作用较苯那普利更显著(P<0.05);两治疗组的血、尿 NO水平升高( P< 0. 01); TGF-β1 mRNA表达水平下调( P< 0. 001),缬沙坦组更明显( P<0.001)。病理上对照组大鼠肾小动脉壁显著增生肥厚,管腔狭窄甚至闭锁,个别小球硬化;而缬沙坦和苯那普利组的肾小动脉结构正常,未见小球硬化。结论缬沙坦能显著减少尿蛋白,逆转SHR肾小动脉硬化改变,保护肾功能,其机制可能有血管紧张素Ⅱ、NO和TGF-β1参与。
Objective To study the effect of valsartan on renal structure and function in spontaneously hypertensive rat(SHR) and explore its mechanism. Methods Twenty SHRs were gorged with benazepril (10 mg·kg-1· d -1), valsartan (10 mg· kg-1·d-1) or water respectively for 12 weeks in the treating and control groups. The blood pressure, proteinuria and nitric oxide (NO) were assessed, and renal tissues were examined routinely by light and electron microscopy. The levels of TGF-β1 mRNA were detected by RT-PCR. Results The excretion of proteinuria significantly decreased in the treating groups compared to control group(P < 0. 01), and was further lower in valsartan group(P < 0. 05). The NO levels of serum and urine in the treating groups were significantly higher than that in the control(P < 0. 01). The levels of TGF-β1 mRNA were down-regulated in the treating groups(P < 0. 001), and further lower in valsartan group(P < 0. 001 ). Severe hypertrophy and sclerosis on the walls of arterioles, narrow, even occlusion in the lumina of these arterioles and hyalinization in some glomeruli were seen in control SHR. Benazepril and valsartan could attenuate the above injuries of small arteries. There was no hyalinization in glomeruli and arterioles. Conclusions Valsartan reduces the extent of proteinuria and attenuates functional and structural injuries induced by hypertension. Angiotensin Ⅱ, NO and TGF-β1 may be involved in the mechanism concerned.
出处
《中华肾脏病杂志》
CAS
CSCD
北大核心
2000年第5期316-319,共4页
Chinese Journal of Nephrology
关键词
自发性高血压
缬沙坦
肾损害
保护作用
Rat, spontaneously hypertensive
Angiotensin Ⅱ receptor antagonist
Nitric oxide
Transforming growth factor-β1
Renal arterial sclerosis