中文摘要：

目的：本研究拟应用醛固酮受体拮抗剂干预肥胖致肾损伤小鼠模型，以期初步探讨醛固酮在肥胖相关性肾小球病（obesity-related glomerulonephropathy, ORG）中的作用。方法雄性C57BL/6J小鼠分为：对照组（10只），予10%脂肪含量普通饲料喂养；模型组（10只）和干预组（12只），予60%高脂饲料喂养。8周后，对照组和模型组予60%丙二醇10 ml·kg-1·d-1皮下注射，干预组予螺内酯20 mg·kg-1·d-1皮下注射。检测理化指标及肾组织病理，实时定量PCR及Western印迹检测足细胞标志蛋白的mRNA和蛋白变化。结果与对照组相比，12周末模型组小鼠体质量、肾质量、Lee氏指数、脂肪指数、血三酰甘油、血胆固醇、肌酐清除率、12 h尿蛋白量均明显上升（P＜0.05）；肾小球平均直径及肾小管损伤面积及足突宽度均明显增大（P＜0.05）；肾组织nephrin、podocin、podoplanin、podocalyxin mRNA及蛋白相对表达量下调（P＜0.05）。螺内酯干预后，上述指标均改善。结论醛固酮可损伤足细胞，参与ORG的发生，而抗醛固酮干预可改善上述过程，故为应用醛固酮受体拮抗剂治疗ORG提供了初步实验依据。

英文摘要：

Objective To examine whether aldosterone contribute to obesity related glomerular disease. Methods C57BL/6J mice were randomly divided into three groups： a control group （low-fat-diet, n=10）, a model group （high-fat-diet, n=10） and a intervention group （high-fat-diet, n=12）. After 8 weeks intervention group were treated with a mineralocorticoid receptor antagonist, spirolactone （SPL）.The physicochemical indexes and the renal pathology of the three groups were all detected. The mRNA and protein expressions of podocyte marker protein were determined by real-time PCR and Western blotting, respectively. Results Compared with the control group, body weight, kidney weight, Lee ’s index, fat index, blood cholesterol, blood triglyceride, creatinine clearance rate, urinary protein excretion, glomerular average diameter, glomerular foot process average width were significantly up - regulated （P〈0.05）; The mRNA and protein expression of nephrin, podocin, podoplanin and podocalyxin were significantly down-regulated in model group （P〈0.05）. Meanwhile, these changes were attenuated by SPL. Conclusion Aldosterone can participate in the process of obesity- related renal injury, and these can be attenuated by mineralocorticoid receptor antagonist, spirolactone. This gives us preliminary clues to treat ORG.