斯伐他汀对糖尿病肾病大鼠肾小球系膜细胞p38信号通路的影响

目的研究糖尿病肾病大鼠肾小球系膜细胞p38丝裂原活化蛋白激酶（MAPK）的表达及斯伐他汀对其的影响。方法分别以高糖、糖基化终产物（AGE）及过氧化氢孵育糖尿病大鼠肾小球系膜细胞（RMC），Western印迹法检测RMC的p38MAPK和TGF—β蛋白表达，p38MAPK特异性抑制剂SB203580及斯伐他汀预处理对其影响。结果高糖、AGE及过氧化氢均可单独激活p38MAPK，增加RMC的磷酸化（P）p38MAPK和TGF—β的蛋白表达；SB203580显著抑制TGF—β的蛋白表达（P〈0．05）；斯伐他汀抑制p38MAPK的活化并减少TGF—β的蛋白表达（P〈0．05）。结论p38MAPK可能是糖尿病肾病发生的始动信号之一。斯伐他汀可能通过抑制p38MAPK磷酸化而减少TGF—β的蛋白表达。

Effect of simvastatin on p38 mitogen-activated protein kinase in rat mesangial cells

Objective To investigate the relationship between p38 mitogen-activated protein kinase (p38MAPK) and transforming growth factor-β (TGF-β), and to explore the effect mechanism of p38MAPK on diabetic nephropathy (DN). Methods Rat mesangial cells (RMC) were separately incubated with high glucose, advanced glycosylation end products (AGE) and H2O2 after pre-reatment of SB203580 (p38MAPK special inhibitor) and simvastatin. The protein expression of p-p38MAPK and TGF-β was examined by Western blot. Results Compared to the control group, high glucose, AGE and H2O2 significantly activated p38MAPK and increased the protein expression of p-p38MAPK and TGF-β (P < 0.05). The protein expression of TGF-β was significantly inhibited by SB203580 (P < 0.05). Compared to RMC incubated with corresponding stimulations, p-p38MAPK and TGF-β were expressed at a lower level in RMC pre-treated with simvastatin (P < 0.05). Conclusions p38MAPK may be one of the initial onset signals of diabetic nephropathy. Simvastatin may effectively attenuate DN progression through down-regulating the expression of TGF-β via p38MAPK.