大麻素受体1拮抗药类似物AM251对糖尿病肾病模型大鼠肾组织足细胞损伤的保护作用研究

目的：研究大麻素受体1（CB1）拮抗药类似物AM251对糖尿病肾病模型大鼠肾组织足细胞损伤的保护作用。方法：将大鼠随机分为阴性对照（生理盐水）组、对照1mg／（kg·d）AM251】组、模型组和AM25l干预建模＋1mg／（kg·d）AM251]组，每组10只。后2组建立糖尿病肾病模型，建模成功后腹腔注射相应药物，12周后检测各组大鼠24h尿蛋白量、血肌酐清除率（Ccr）、肾质量／体质量（KW／BW）、血清生化指标和肾组织中CBl和肾组织足细胞裂隙蛋白Nephrin、Podocin蛋白的表达，并观察肾组织和足细胞病理变化。结果：与阴性对照组比较，对照组大鼠各检测指标差异无统计学意义（P〉0．05），模型组和AM251干预组大鼠24h尿蛋白量、KW／BW、血清生化指标和肾组织中CBl表达均明显增加（P〈0．05），Ccr和足细胞中Nephrin、Podocin蛋白表达均明显降低（P〈0．05）；与模型组比较，AM25l干预组大鼠24h尿蛋白量、KW／BW明显降低（P〈0．05），Ccr和足细胞中Nephrin、Podocin蛋白表达均明显增强（P〈0．05），其余组间差异无统计学意义（P〉0．05）。阴性对照组和对照组大鼠肾组织和足细胞形态正常，模型组大鼠肾组织和足细胞有明显糖尿病肾病的病理改变，AM251干预组大鼠糖尿病肾病的病理改变较模型组均改善。结论：AM251对糖尿病肾病模型大鼠足细胞病变具有保护作用，部分机制可能与上调足细胞中Nephrin、Podocin蛋白的表达有关。

Protective Effects of Cannabinoid Receptors 1 Antagonist Analogs AM251 on Kidney Podocyte Lesions in Dia- betic Nephropathy Rats

OBJECTIVE： To explore the protective effect of cannabinoid receptors 1 （CB1） antagonist analogs AM251 on the podocyte lesions in rats with diabetes nephropathy. METHODS： SD rats were randomized into negative control group, control group 1 mg/（kg.d） AM251], model group and AM251 intervention group modeling＋l mg/（kg.d） AM251] with 10 rats in each group. Diabetes nephropathy model was induced in latter 2 groups, and relevant medicine was injected intraperitoneally after model- ing. After 12 weeks, 24 h urine protein, Ccr, KW/BW, serum biochemical indicator were determined; the expressions of CB1 re- ceptors, Nephrin and Podocin protein in renal tissue were evaluated, and pathological change of renal tissue and podocyte were ob- served. RESULTS： Compared with negative control group, the lab index of rats had no significant change in control group （P〈 0.05）; 24 h urine protein, KW/BW, serum biochemical indicator and the expressions of CB1 receptors increased significantly （P〈 0.05） while the expression of Nephrin and Podocin protein decreased significantly （P〈0.05） in model group and AM 251 interven- tion group; the level of Ccr decreased significantly in model group （P〈0.05）. Compared with model group, 24 h urine protein and KW/BW decreased significantly in AM251 intervention group （P〈0.05）;the level of Ccr and the expression of Nephrin and Podo- cin protein increased significantly （P〈0.05）; other index had no significant difference between 2 groups （P〉0.05）. The morpholo- gy of renal tissue and podocyte were normal in negative control group and control group; significant pathological change of diabe- tes nephropathy was found in renal tissue and podocytes of rats in model group; compared with model group, pathological change of diabetes nephropathy was improved in AM251 intervention group. CONCLUSIONS： AM251 may exert the protective effect on podocytes in diabetic nephropathy rats, and the mechanism may be associated with the up-regulated expression of Nephrin and Podocin protein.