糖尿病肾病大鼠金属硫蛋白的表达及意义
Study on metallothionein expression in rats with diabetic nephropathy kidney
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摘要:目的 探讨金属硫蛋白(metallothionein, MT)在糖尿病肾病大鼠肾脏组织中的表达及意义。方法 链脲佐菌素(STZ)尾静脉注射诱导糖尿病肾病, 分别在诱导2, 4, 8, 16周杀鼠, 取血及肾脏进行研究, 生化方法检测血、尿各项生化指标, 免疫组化方法观察肾脏MT-1蛋白表达, RT-PCR观察MT-1 mRNA及氧化、炎症、纤维化相关细胞因子mRNA表达。结果 随着糖尿病病程进展, 大鼠表现血糖、血肌酐、尿蛋白及肾重与体重比逐渐增高, 病理学检查见糖尿病8周组大鼠肾脏肾小管纤维结缔组织增生明显, 16周组大鼠肾脏显示明显纤维化。免疫组化研究发现在正常组大鼠肾脏有少量MT-1表达, 糖尿病肾病大鼠肾脏MT-1表达明显增多, 差异有统计学意义(P < 0.05), 且随病程而逐渐增加。RT-PCR结果显示, 16周糖尿病大鼠肾脏MT-1、TNF-α、MIP-1、COX2、TGF-β, PAI-1, Col-3等mRNA表达均出现明显上调(P < 0.05)。结论 MT-1在糖尿病大鼠肾脏表达增高是糖尿病肾病病变过程中的一种变化趋势, 可能与细胞因子、抗氧化作用有关, 推测是细胞的重要防御机制之一。Abstract:Objective To study the metallothionein(MT-1)expression in diabetic nephropathy kidney of rats induced by streptozotosin(ST Z).Methods Rats were induced diabetic nephropathy using STZ tail intravenous injection.The immuno-chemical and RT-PCR technique were used to study the MT-1 protein and mRNA expressions in the kidney tissues of normal and diabetic nephropathy rats.Results Weak MT-1 expression was detected in normal renal tissues while strong MT-1 staining was detected in renal tissues of diabetic nephropathy(P < 0105).The MT-1 protein expression was increased with the development of diabetic nephropathy.The expression of MT-1, TNF-A, MIP-1, COX2, TGF-B, PA-I1, Col-3 mRNA increased in renal tissues of 16 weeks diabetic nephropathy rats.(P < 0.05).Conclusion Both MT-1 mRNA and protein expression were increased in ST Zinduced diabetic nephropathy rats indicated that MT-1 might be play an important role in pathophy siology process of diabetic nephro pathy development.It might be relative to oxidize-injure and might be one of cellular defense reactions.
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