血管紧张素Ⅱ输注诱导肾小球ILK表达改变和肾小球损伤

AngiotensinII infusion induced the alteration of ILK expression and glomerular damage

目的观察血管紧张素II（AngII）输注及替米沙坦治疗对大鼠肾小球整合素蛋白激酶（Integrin-linked kinase，ILK）表达的影响，探讨AngII和ILK在肾小球损伤中的作用。方法将18只雄性SD大鼠随机分为3组：A组为对照组，由生理盐水代替AngII；B组用AngII以400ng·kg^-1·min^-1持续输注14d；C组在B组基础上加用替米沙坦30mg·kg^-1·d^-1进行干预。每组6只。每周末测量尾动脉收缩压、24h尿蛋白定量，于14d处死动物。心脏采血，检测血肌酐（SCr）；留取肾组织，行PAS染色，光镜下观察肾组织病理学改变；免疫组织化学法、RT-PCR及Western印迹法检测ILK表达。结果①AngII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，替米坦治疗可以明显降低血压和减少尿蛋白（P〈0．05），减轻肾小球系膜区增生（P〈0．01）。②AngⅡ输注14d时，ILK表达显著增加，替米沙坦治疗可显著降低ILK表达（P〈0．05）。结论肾脏ILK表达升高可能是AngII引起肾脏损害的重要机制。

Objective To observe the effect of angiotensin II （Ang II ） infusion and telmisartan treatment on the expression of the integrin linked kinase（ILK）, and the relationship between Ang II and ILK in the glomerular damage. Methods The male Sprague Dawley rats were randomly divided into 3 groups： A, control group with 0. 9% saline solution; B, Ang II was infused by 400 ng· kg^-1 ·min^-1 for 14 days;C,Telmisartan treatment at a dose of 30 mg.kg ^-1·d^-1 on the basis of group B （6 rats in each group）. The systolic blood pressure was measured and the 24 h urine sample was collected for detection of proteinuria at every weekend. Animals were sacrificed at the day 14. Serum creatinine was determined from cardiac blood,and renal pathological changes were observed under a light microscope. The expression of ILK mRNA and protein was detected by RT-PCR, Western blot, and immuno- histochemical staining. Results （1） Systolic blood pressure, proteinuria and mesangial proliferation were increased with time after infusion of Ang II , and these changes could be antagonized with telmis arran treatment （P〈0. 05）. （2）The expression of ILK mRNA and protein was increased significantly after infusion of AngII for 14 days,but that was inhibited by telmisartan treatment （P〈0. 05）. Conclusions Overexpression of ILK may be an important mechanism in AngII induced renal damage.