系膜增生性肾炎大鼠肾小球周期素激酶抑制剂P27的变化及意义

Changes of cyclin kinase inhibitor P27 in glomerulus of Thy1 glomerulonephritis in rats

目的 :探讨周期素激酶抑制剂 P2 7在系膜增生性肾炎模型 Thy1肾炎大鼠系膜细胞 (MC)增生中的作用。 方法 :利用抗胸腺细胞抗体制成 Thy1肾炎模型 ,Western印迹法测定肾小球裂解液 P2 7蛋白水平 ,RT- PCR方法测定肾小球 P2 7m RNA,EL ISA方法测定肾小球裂解液细胞外基质 (ECM)蛋白 (纤维连接蛋白及 型胶原 )。 结果 :Thy1肾炎第 1天 P2 7水平即有明显下降 ,第 3天 (MC增生最为明显 ) P2 7水平最低 ,第 5天 (MC增生开始消散 ) P2 7水平有所回升 ,提示 P2 7水平与MC增生程度有关 ;Thy1肾炎第 3天肾小球 P2 7m RNA与正常对照组比较无明显差别 ;而 Thy1肾炎大鼠肾小球纤维连接蛋白和 型胶原均升高 (P<0 .0 1) ,在第 3天达峰值 ,第 5天略有回降 ,但仍显著高于正常对照组 (P<0 .0 1)。结论 :P2 7水平下降可能在 Thy1肾炎 MC增生中起重要作用。

Objective: To investigate the role of cyclin kinase inhibitor P27 on the proliferation of mesangial cell(MC) in Thy1 glomerulonephritis(GN) rats. Methods: The Thy1 model of experimental mesangial proliferative glomerulonephritis was induced by intravenous injection of rabbit anti-thymocyte plasma. The P27 protein of glomerular lysate was detected with Western blotting analysis. The P27 mRNA was determined with RT-PCR. The extracellular matrix (ECM) protein (fibronectin and type Ⅳ collagen) of glomerular lysate was examined with ELISA. Results: Glomerular P27 protein of Thy1 model rat decreased compared with that of normal rat. The level of P27 was associated with the degree of MC proliferation:P27 began to decrease on day 1 in Thy1 model, then reached the lowest on day 3 when MC proliferation was maximal, then returned to 60% of the baseline level on day 5 when MC proliferation began to resolute. Glomeruar P27 mRNA remained constant in Thy1 GN(3 d) rats. Glomerular fibronectin(Fn) and type Ⅳ collagen increased in Thy1 model: They reached the highest on day 3(P<0.01), and decreased on day 5(but they were higher than those of normal rat). Conclusion: Low level of P27 may play an important role in the MC proliferation of Thy1 glomerulonephritis rat.