缬沙坦对Thy-1肾炎大鼠肾小球系膜细胞P27表达的影响

Effect of valsartan on P27 expression in mesangial cells of Thy1 glomerulonephritis rats

目的 观察Thy 1肾炎大鼠系膜细胞增生及P2 7表达 ,以及血管紧张素Ⅱ受体拮抗剂缬沙坦对其干预作用。方法 设正常组、Thy 1肾炎组及Thy 1肾炎 +缬沙坦治疗组。分别于各组疾病诱导后第 1、3、5、7d取肾脏行病理检查 ,免疫组化检测肾小球内PCNA、P2 7蛋白的表达 ,Westernblot分析肾小球内P2 7的表达。结果 在正常大鼠系膜细胞P2 7存在高表达 ,而在肾炎大鼠随系膜细胞增生 ,其P2 7表达减少。缬沙坦治疗组第 3～ 7d肾小球系膜细胞增生、系膜区扩张程度以及肾小球内PCNA表达低于肾炎组 (P <0 .0 5 ) ,而肾小球内P2 7表达高于肾炎组相应时间点 (P <0 .0 5 )。结论 肾小球系膜细胞非增殖状态的维系与其P2 7的高表达相关 ,缬沙坦可维持系膜细胞P2 7的高表达 ,抑制系膜细胞增殖及系膜扩张。提示缬沙坦对Thy

Objective To observe P27 expression and proliferation of mesangial cells of rats with Thy1 glomerulonephritis and to evaluate the interfering effect of valsartan, a specific angiotensin Ⅱ receptor antagonist, on Thy1 glomerulonephritis. Methods Rats were divided into normal control group, Thy1 glomerulonephritis group and valsartan treatment group. Following the onset of glomerulonephritis, renal morphological changes were observed on days 1, 3, 5 and 7, and proliferating cell nuclear antigen(PCNA) and P27 expression in glomerulus were measured by immunohistochemistry and Western blotting. Results High expression of P27 was found in quiescent mesangial cells of normal rats, but decreased expression in mesangial cells of rats with Thy1 glomerulonephritis, accompanying with the proliferation of mesangial cells. In valsartan treatment group, glomerular hypercellularity, mesangial matrix expansion and PCNA expression were significantly reduced as compared with those of the untreated rats with Thy1 glomerulonephritis from day 3 to day 7( P <0 05), but P27 expression in glomeruli was higher than that in Thy1 glomerulonephritis group. Conclusion The maintenance of non proliferation of mesangial cells is related with the high expression of P27. Valsartan can inhibit the proliferation of mesangial cells and the mesangial matrix expansion by means of keeping the high expression of P27, suggesting that valsartan has a certain therapeutic effect on Thy1 glomerulonephritis rats.