细胞周期蛋白D_1在阿霉素诱导大鼠慢性进行性肾脏损害模型中的表达及罗格列酮干预效应

The expression of cyclin D1 in renal tissue of rats with adriamycin induced chronic kidney disease and the effects of rosiglitazone intervention

目的研究细胞周期蛋白D1(cyclin D1)在阿霉素诱导大鼠慢性进行性肾脏损害模型中的表达,以及罗格列酮(RSG)干预对其表达的影响,探讨RSG肾脏保护效应的可能机制。方法 45只2月龄SD大鼠随机分成对照组、肾损害组、RSG干预组。肾损害组和RSG干预组从尾静脉注射阿霉素(ADR)6 mg/kg建立肾病模型,对照组注射生理盐水。2周后,RSG干预组给予RSG(4 mg/kg)灌胃,对照组和肾损害组给予等量蒸馏水灌胃。模型建立当天、第14天、70天分别收集24 h尿测尿蛋白;模型建立第70天取血测肝肾功能、电解质、血糖,苏木素-伊红染色观察肾脏病理学改变,免疫组化及RT-PCR测定cyclin D1表达。结果 RSG干预组24 h尿蛋白定量、血清白蛋白、三酰甘油、胆固醇水平,系膜细胞和成纤维细胞cyclin D1蛋白及mRNA表达量与肾损害组比较,差异均有统计学意义(P均<0.05)。病理学观察,RSG干预组大鼠的肾脏损害较肾损害组轻。结论 RSG可减轻阿霉素诱导的肾损害。RSG下调肾脏系膜细胞及成纤维细胞cyclin D1表达可能是其肾保护机制之一。

objective To detect the expression of eyclin Dl in renal tissue of rats with adriamycin （ADR） induced chronic kidney disease （CKD） and the effects of rosiglitazone （RSG） intervention, to explore the possible mechanisms of renoprotective effects of RSG. Methods Forty-five SD rats, 2 months old, were randomly divided into three groups, control group, model group, and RSG intervention group. ADR （6 mg/kg） was injected through the tail vein of rats in model group and RSG intervention group for production of CKD animal model. The normal saline was injected in control group. After two weeks, RSG intervention group received RSG （4 mg/kg） via nasogastric garage; control group and model group received same amount of distill water. The 24 hours urine was collected for measurement of urine protein at ADR injection, and after injection 14 and 70 days. After ADR injection 70 days, the blood was collected for detecting liver and kidney function, electrolytes, and glucose. The pathological change of kidneys was observed. The expression of cyclin D1 was examined with immunohistochemistry and RT-PCR. Results Compare with model groups, 24 hour urinary protein .excretion, the level of serum albumin, triglyceride and cholesterol, and the expression of cyclin D1 in mesangial cells and fibroblastsis were significantly different in RSG intervention group （all P 〈 0.05）. Pathological damage was slighter in RSG intervention group than that in model group. Conclusions RSG can reduced kidney damage induced by ADR. RSG intervention reduced the expression of eyclin D1 in mesangial cells and fibroblasts may be one of the mechanisms of renal protection by RSG.