摘要
目的 本文旨在研究线粒体靶向抗氧化剂SKQ1对糖尿病(DM)小鼠肾损伤的影响,以阐明SKQ1对肾脏的保护作用及机制.方法 选取野生型雄性C57BL/6小鼠30只,行右侧肾切除术后注射诱导DM模型,分成对照组、DM组、SKQ1组各10只.用药组每天饮用SKQ1水溶液,对照组和DM组正常饮水.连续饲养28周后,收集尿液测尿微量白蛋白的变化;通过HE和PAS染色法观察小鼠肾脏病理结构和肾脏纤维化的变化;通过q-PCR和免疫荧光法检测小鼠NPHS2、WT1、Podxl、desmin、α-SMA表达情况.结果 与对照组比较,DM组小鼠尿微量白蛋白明显增加;与DM组小鼠比较,SKQ1组小鼠尿微量白蛋白降低.HE和PAS染色结果显示,与对照组比较,DM组小鼠肾小球系膜细胞增多,细胞外基质增生,有明显的胶原纤维沉积;与DM组比较,SKQ1组小鼠肾小球系膜细胞数量减少,细胞外基质增生减轻,胶原纤维沉积明显减轻.q-PCR和免疫荧光结果显示,与对照组比较,DM组小鼠足细胞相关分子NPHS2、WT1、Podxl明显降低,desmin、α-SMA表达量增加;与DM组比较,SKQ1组小鼠足细胞相关分子NPHS2、WT1、Podxl表达明显增加,但desmin、α-SMA表达量下降.结论 SKQ1可上调NPHS2、WT1、Podxl的表达及下调desmin、α-SMA的表达来减轻足细胞损伤,改善小鼠尿微量白蛋白排泄和肾小球纤维化,进而延缓糖尿病肾病(DN)的进展.
Abstract
Objective To investigate the effect of mitochondrial targeted antioxidant SKQ1 on renal injury in diabetes mellitus(DM)mice,so as to clarify the protective effect and mechanism of SKQ1 on kidney.Methods Thirty wild type male C57BL/6 mice were selected to induce the diabetes model after right nephrectomy.They were divided into the control group,the DM group and the SKQ1 group with 10 mice in each group.The SKQ1 group drank SKQ1 aqueous solution daily,while the control group and the DM group drank water.After 28 weeks of continuous feeding,urine was collected to measure changes in urinary mi-croalbumin levels.HE and PAS staining methods were used to observe the pathological structure and renal fibrosis changes of mice kidneys.q-PCR and immunofluorescence methods were used to detect the expression of NPHS2,WT1,Podxl,desmin,andα-SMA in mice.Results Compared with the control group,the DM group mice showed a significant increase in urinary mi-croalbumin.Compared with the DM group mice,the SKQ1 group mice showed a decrease in urinary microalbumin.The HE and PAS staining results showed that compared with the control group,the DM group mice had an increase in glomerular mesangial cells,proliferation of extracellular matrix,and significant deposition of collagen fibers.Compared with the DM group,the SKQ1 group mice showed a decrease in the number of glomerular mesangial cells,a reduction in extracellular matrix proliferation,and a significant reduction in collagen fiber deposition.The q-PCR and immunofluorescence results showed that compared with the control group,the DM group mice showed a significant decrease in podocyte related molecules NPHS2,WT1,and Podxl,while the expression levels of desmin and α-SMA increased.Compared with the DM group,the expression of foot cell related molecules NPHS2,WT1,and Podxl in the SKQ1 group mice significantly increased,but the expression levels of desmin and α-SMA de-creased.Conclusion SKQ1 can up-regulate the expression of NPHS2,WT1,Podxl and down-regulate the expression of desmin and α-SMA to alleviate podocyte injury,improve the excretion of urinary microalbumin and glomerular fibrosis in mice,and then delay the progress of diabetes nephropathy.
维普
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