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目的探讨咪唑立宾对急性Thy1肾炎大鼠肾小球系膜细胞增殖的影响及其作用机制。方法 15只雄性Wistar大鼠随机分为对照组、Thy1肾炎模型组(模型组)及咪唑立宾治疗组(MZ组),各5只。应用考马斯亮蓝法检测24h尿蛋白定量,PAS染色评估系膜细胞增殖,RT-PCR检测血小板源生长因子-β的基因表达水平,Western blot检测血小板源生长因子-β的蛋白表达水平。结果与对照组比较,模型组24h尿蛋白明显增多(P<0.05),系膜细胞明显增殖,细胞外基质大量积聚(P<0.05),血小板源生长因子-β的mRNA及蛋白量高度表达(P<0.05);与模型组比较,MZ组24h尿蛋白明显减少(P<0.05),系膜细胞增殖及细胞外基质大量积聚程度明显减轻(P<0.05),血小板源生长因子-β的mRNA及蛋白质的表达明显下降(P<0.05)。结论咪唑立宾能明显抑制急性Thy1肾炎大鼠系膜细胞增殖,减少尿蛋白,其对急性Thy1肾炎的治疗作用至少部分是通过下调血小板源生长因子-β的表达实现的。
Objective To investigate the effects of midazolam on the proliferation of glomerular mesangial cells in rats with acute Thy1 nephritis and its mechanism. Methods Fifteen male Wistar rats were randomly divided into control group, Thy1 nephritis model group (model group) and mizoribine treatment group (MZ group), each with 5 rats. The proteinuria of 24-hour urine was detected by Coomassie brilliant blue staining. The mesangial cell proliferation was evaluated by PAS staining. The gene expression of platelet-derived growth factor-β was detected by RT-PCR. The protein expression of platelet-derived growth factor-β was detected by Western blot. Results Compared with the control group, the expression of 24 h urinary protein in the model group was significantly increased (P <0.05), the mesangial cells were significantly proliferated, the extracellular matrix was greatly accumulated (P <0.05), and the mRNA and protein level of platelet-derived growth factor- (P <0.05). Compared with model group, 24h urinary protein in MZ group was significantly decreased (P <0.05), mesangial cell proliferation and accumulation of extracellular matrix were significantly reduced (P <0.05), mRNA of platelet-derived growth factor- And protein expression decreased significantly (P <0.05). Conclusion Mizolabine can significantly inhibit the proliferation of mesangial cells in rats with acute Thy1 nephritis and reduce the urinary protein. The therapeutic effect of mizoribine on acute Thy1 nephritis is at least partly mediated by the down-regulation of platelet-derived growth factor-β.