缬沙坦对自发性高血压大鼠肾脏结构与功能的保护作用

Nephroprotection of valsartan on function and morphology in spontaneously hypertensive rats

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.