替米沙坦对高血压大鼠Podocalyxin表达的影响及作用

Effects of Telmisartan on Podocalyxin Expression in the Kidney of Hypertensive Rats

目的:探讨替米沙坦对高血压大鼠肾组织podocalyxin(PCX)表达的影响及作用。方法:30只雄性SD大鼠随机分为高血压组(A组)、替米沙坦组(B组)、对照组(C组)。以改进的"两肾一夹"方法建立高血压大鼠模型。B组从造模后5周始给予替米沙坦5mg·kg^(-1)·d^(-1)混悬液灌胃,共用药6周。观察收缩压(SBP),分别于实验前、用药前、用药后6周检测3组大鼠的尿β_2-微球蛋白(β_2-MG)、血尿素氮(BUN)及血肌酐(Scr)水平;免疫组化方法观察PCX在肾组织的表达,并分析PCX的积分吸光度(IA)值;观察肾脏病理及足细胞超微结构改变。结果:用药前A组及B组SBP较C组显著升高(P<0.01);用药后B组SBP较A组显著降低(P<0.01)。A组β_2-MG显著高于C组(P<0.01);用药后B组尿β_2-MG显著低于A组(P<0.01),3组BUN、Scr在整个实验过程中无显著差异。A组、B组肾脏发生病理及足细胞超微结构改变。经替米沙坦治疗后,B组肾脏病理变化及足细胞超微结构改变均有缓解。并可上调PCX蛋白的表达。结论:替米沙坦可减少蛋白尿,缓解高血压肾损害和足细胞损伤。并可上调PCX蛋白的表达从而发挥保护足细胞的功能。

To investigate the effects of telmisartan on podocalyxin （PCX） expression in the kidney of hypertensive rats. Method： Thirty male SD rats were randomly divided into hypertension group （group A） ,telmisartan group （group B） and control group （group C）. Modified ＂two renal a cllp＂ method was used to establish hypertension model in the rats. After 5 weeks, the rats in group B were given telmisartan suspension with the close of 5 mg. kg - 1 . d - 1 by intragastric administration, and the period of drug ad- ministration was 6 weeks. The systolic blood pressure （SBP） ,urinary β2-microglobulin （β2-MG） ,blood urea nitrogen （BUN） and serum creatinine （Scr） were monitored before the experiment, before drug administration and at 6 weeks after drug administration, respectively. The podocalyxin expression in the kidney was detected by immunohistochemistry, and the IA value of PCX was also analyzed. The pathological changes of the kidney and uhrastructure of podocytes were observed under optical and electron microscope, respectively. Result ： The systolic blood pressure in group A and group B was significantly higher than that in group C before drug administration （ P 〈 0. 01 ） ,and that in group B was significantly lower than that in group A after drug administration （P 〈0. 01 ）. The urinary β2-MG in group A was significantly higher than that in group C before drug administration （ P 〈 0. 01 ） , and that in group B was significantly lower than that in group A after drug administration （ P 〈 0. 01 ）. However, the BUN and Scr levels in three groups had no significant difference in the whole process. Pathological and the ultrastructure of podocytes changes in the kidney from group A and group B could be observed under optical and electron microscope. After telmisartan treatment in group B ,pathological and ultrastructure of podocytes changes in the kidney were both alleviated. The expression of PCX in group A was significantly reduced, and the IA value was significantly lower than that of group C （P 〈 0. 01 ）, while PCX expression was enhanced in group B. Conclusion： Telmisart＇an can reduce albuminaria, alleviate hypertensive renal impairment and podocvte damage, and raise PCX protein expression in order to protect podocyte function.