缬沙坦对自发性高血压大鼠肾脏的保护作用

Protective effects of valsartan on kidneys of spontaneously hypertensive rats

目的探讨缬沙坦对自发性高血压大鼠(SHR)肾脏的保护作用,以及与结缔组织生长因子(CTGF)在SHR肾脏中表达的关系。方法本实验以12周龄雄性SHR和同龄雄性WistarKyotoRats(WKY)大鼠为研究对象,SHR分为治疗组[缬沙坦,30mg/(kg·d)、灌胃]与对照组,WKY大鼠为正常对照组,测量不同时期(12周,24周)大鼠尾动脉压、肾功能、尿β2微球蛋白(β2MG)的变化情况,以及用免疫组化的方法观察结缔组织生长因子在肾脏中的表达。结果12周后,相对于同龄WKY大鼠、SHR治疗组而言,SHR对照组的尿素氮、血肌酐变化无显著意义,而尾动脉压、尿β2MG均有显著增高(P<0.01,P<0.05)。经免疫组化半定量检测显示:在24周龄SHR对照组,其肾脏中CTGF的表达相对于同龄WKY大鼠及SHR治疗组明显升高(P<0.01),同时与尿β2MG的水平成正比(P<0.05)。结论缬沙坦能显著减少尿蛋白,同时使CTGF在SHR肾脏的表达明显减少,说明CTGF可能是慢性高血压导致的肾损害的重要机制之一。

Objective To observe the renoprotective effect of valsartan and to examine the expression of connective tissue growth factor (CTGF) in the kidney of spontaneously hypertensive rats(SHR). Methods The SHR were randomly assigned to control group and valsartan treatment group. Valsartan treatment group was gorged with valsartan 30 mg/(kg·d). Wistar-Kyoto Rats(WKY) served as normal control, whose blood pressure, urinary β_2-microglobulin, Bun, and Scr were measured at 12-week old and 24-week old respectively. At the end of experiment, the renal expression of CTGF was determined. Results Twelve weeks later, in the SHR control group, except Bun and Scr,the blood pressure and urinary β_2-microglobulin, significantly increased compared with those of the other two groups(P<0.01,P<0.05). Semi-quantitative assessment of the immune-histochemical staining showed that: Renal expression of CTGF in SHR control group significantly increased compared with that in WKY group and treatment group(P<0.01). At the same time, the expression of CTGF was also found positively related with the increasing of urinary β_2-microglobulin (P<0.05). Conclusions Valsartan not only significantly reduces the extent of proteinurina of SHR, but also decreases the expression of CTGF in the kidney of SHR. CTGF may be involved in inducement of this renal disease.