亚硒酸钠对糖尿病肾病大鼠肾脏脂联素和nephrin表达的影响

目的 探讨亚硒酸钠对糖尿病肾病大鼠肾脏脂联素和nephrin表达的影响及其相互间的关系,从而研究亚硒酸钠与脂联素、nephrin在糖尿病肾病中的作用机制.方法 通过链脲佐菌素法加高脂饮食诱导模拟大鼠糖尿病肾病模型,实验设完全空白对照组、糖尿病组、糖尿病药物干预组,药物干预组每日给予亚硒酸钠溶液灌胃,其它组给予等量盐水溶液灌胃.10周后处死大鼠,取血、尿标本测相关生化指标,取肾脏组织分别提取DNA和蛋白质标本,石蜡切片光镜观察病理改变及免疫组化分析蛋白表达定位,实时定量PCR法检测脂联素mRNA表达、RT-PCR法检测nephrin mRNA表达,Western印迹法检测脂联素和nephrin蛋白表达.结果 亚硒酸钠干预组大鼠生化指标较糖尿病组明显改善,光镜下观察亚硒酸钠干预组病理改变较糖尿病组明显减轻.免疫组化分析,亚硒酸钠干预组脂联素蛋白着色较糖尿病组明显增强,且肾小管、肾小球内均有着色;糖尿病组nephrin蛋白表达着色较空白对照组减少,亚硒酸钠干预组较糖尿病组着色明显增多.亚硒酸钠干预组脂联素mRNA和蛋白表达明显高于糖尿病组和正常对照组,差异有统计学意义(均P＜0.05).亚硒酸钠干预组nephrin mRNA和蛋白表达均较糖尿病组明显增加,但仍较空白对照组降低,差异均有统计学意义(P＜0.05).结论 亚硒酸钠能促进大鼠肾脏脂联素和nephrin表达,表明亚硒酸钠、脂联素和nephrin在延缓和防治糖尿病肾病的发生发展中可能起重要作用.

Influence of sodium selenite on the expression of adiponectin and nephrin in the kidney of rats with diabetic nephropathy

Objective To investigate the influence of sodium selenite on the expression of adiponectin and nephrin in the kidney of rats with diabetic nephropathy, the relation of sodium selenite with adiponectin and nephrin, and to study the roles played by these factors in diabetic nephropathy. Methods Rat models of diabetic nephropathy were established by injecting intraperitoneally streptozocin combined with high fat diet. Three groups of rats were employed: control group, diabetic nephropathy group, and selenite-treated group. The selenite-treated rats were given selenite solution by intragastric administration every day, and other groups were given same volume of saline. After 10 weeks, all rats were sacrificed, blood and urine samples were collected. The kidneys were used to observe pathological changes with light microscope, and to locate protein expression with immunohistochemistry analysis. The mRNA and protein expressions of adiponectin and nephrin were analyzed via real-time PCR, RT PCR, and Western blot. Results The basic condition, biochemical parameters, and pathological images in selenite-treated group were better than those in diabetic nephropathy group. Immunohistochemistry analysis showed that the expression of adiponectin was in both glomeruli and renal tubules in selenite-treated group, and the coloration was enhanced as compared with diabetic nephropathy group. The mRNA and protein expressions of adiponectin in selenite-treated group were significantly higher than those in diabetic nephropathy group and the control group (all P＜0. 05 ). Nephrin expression in selenite-treated group was also higher than that in diabetic nephropathy group, but lower than that in control group. Conclusion Sodium selenite can enhance the mRNA and protein expressions of adiponectin and nephrin in kindey of rats with diabetic nephropathy. Sodium selenite,adiponectin, and nephrin may play important roles in delaying and preventing the development of diabetic nephropathy.