目的观察血管紧张素Ⅱ输注大鼠模型肾小球小凹蛋白-1表达及分布,探讨小凹蛋白-1在肾小球损伤中的作用。方法18只雄性Wistar大鼠皮下埋置渗透性微泵,随机分为3组。A组为正常对照组,由生理盐水代替血管紧张素Ⅱ。B组用血管紧张素Ⅱ以400ng·kg^-1·min^-1持续输注28d。C组在B组基础上加用替米沙坦3mg·kg^-1·d^-1进行干预。每周末测量尾动脉收缩压、24h尿白蛋白定量,于28d处死大鼠。心脏采血,检测血肌酐。留取肾组织,光镜、电镜下观察肾组织病理学改变。免疫组织化学法、免疫荧光分别检测肾小球小凹蛋白-1表达及小凹蛋白-1磷酸化水平。结果(1)血管紧张素Ⅱ输注后,大鼠血压逐渐升高,尿蛋白持续增加,肾小球系膜区增生加重,替米沙坦治疗可以明显降低血压和减少尿蛋白,减轻肾小球系膜区增生。(2)血管紧张素Ⅱ输注大鼠肾小球小凹蛋白-1表达无明显改变,但其磷酸化水平明显增高,替米沙坦干预后小凹蛋白-1磷酸化水平明显降低。结论小凹蛋白-1在血管紧张素Ⅱ诱导肾损伤中可能发挥重要作用。
Objective To evaluate the expression of the caveolin-1 in angiotensiⅡ-infused glomerular injury in rats, and investigate the possible effect of caveolin-I on the glomerular damage. Methods Eighteen male Wistar rats were randomly divided into 3 groups:nomal control group, AngⅡ infusion group and AngⅡ infusion plus Telmisartan administration group, and all the rats were subcutaneously embedded with osmotic minipumps. The pumps in rats of AngH infusion group and Telmisartan administration group were filled with AngⅡ at a speed of 400 ng · kg^-1. min^-1 for 4 weeks, which was substituted with 0. 9% saline solution in pumps of control animals. The rats in Telmisartan administration group were administrated with Telmisartan (3mg· kg^-1 · day^-1 ). The systolic blood pressure was measured and the 24-h urine samples were collected for detection of proteinuria at every weekend. Animals were sacrificed at the day 28. Serum creatinine was determined in cardiac blood, and renal pathological changes were observed under a light microscope and electron microscope. The expression of caveolin-1 and phosphorated caveolin-1 was detected by using immunohistochemical staining and immunofluorescence method respectively. Results AngⅡ infusion induced high blood pres- sure, proteinuria and mesangial proliferation, which were alleviated with telmisartan treatment. The expression of total caveolin-1 protein in glomeruli was comparable among the three groups, however, the glomerular p-caveolin-1 expression in AngⅡ-infused rats was increased significantly as compared with that in control rats. Telmisartan treatment greatly decreased the p-caveolin expression (P〈0. 05). Conclusions Caveolin-1 may be involved in the progression of Ang Ⅱ-induced glomerular damage.