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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抑制作用及其对细胞周期调控蛋白Cyclin D1的影响。方法 54只雄性Wistar大鼠随机分为对照组、Thy1肾炎模型组和咪唑立宾组各18只。模型组与咪唑立宾组尾静脉注射OX-7细胞上清浓缩液制备急性Thy1肾炎模型,对照组注射等量生理盐水。注射后6h灌胃给药,对照组与模型组给予蒸馏水,咪唑立宾组给予咪唑立宾20mg/kg,连续给药7d后,检测3组24h尿蛋白定量,采用PAS染色评估肾脏组织病理改变,应用RT-PCR法检测Cyclin D1基因表达情况,应用Western blot法检测Cyclin D1蛋白表达情况。结果模型组24h尿蛋白定量、肾小球内细胞数、Cyclin D1mRNA及Cyclin D1蛋白表达水平均明显高于对照组和咪唑立宾组(P<0.05)。结论咪唑立宾通过调控细胞周期调节蛋白Cyclin D1抑制急性Thy1肾炎大鼠系膜细胞增殖,减少尿蛋白。
Objective To investigate the inhibitory effect of midazolam on the proliferation of glomerular mesangial cells in rats with acute Th1 nephritis and its effect on the expression of cyclin D1. Methods Fifty-four male Wistar rats were randomly divided into control group, Thy1 nephritis model group and mizoribine group. Acute Thy1 nephritis model was induced by injection of OX-7 cell supernatant concentrate into the model group and the midazolam group, while the control group was injected with the same amount of saline. The rats in the control group and model group were administered with distilled water at 6h after injection, and the mice in the midazolam group were given mizoribine 20mg / kg. After being administered for 7 days continuously, the urinary protein excretion of three groups was measured. The pathological changes of kidney tissue were evaluated by PAS staining The expression of Cyclin D1 gene was detected by RT-PCR. The protein expression of Cyclin D1 was detected by Western blot. Results 24h urinary protein, glomerulus cells, Cyclin D1 mRNA and Cyclin D1 protein expression levels were significantly higher than the control group and the midazolam group (P <0.05). Conclusion Mizoribin can inhibit the proliferation of mesangial cells in rats with acute Thy1 nephritis by regulating the cell cycle regulatory protein Cyclin D1 and decrease the urinary protein.