目的 评价GLP-1受体激动剂利拉鲁肽对肥胖相关性肾病( ORG)小鼠模型的作用,以及与自噬通路 SIRT-1/AMPK 的关系.方法 选取34只雄性小鼠,随机分为正常对照组12只,高脂组22只,高脂组随机分为利拉鲁肽组(利拉鲁肽干预)及肥胖组(生理盐水干预),干预12周后,进行肾脏病理学染色、血清学及尿液指标检测,采用Western blot法检测肾脏组织自噬通路蛋白表达量,采用方差齐性检验分析数据.结果 与正常对照组相比,肥胖组小鼠肾小球肥大、系膜基质增多明显,且伴有局灶节段性硬化,与肥胖组相比,利拉鲁肽组小鼠肾脏病变明显减轻.与正常对照组相比,肥胖组小鼠的体质量、右肾湿重、尿微量白蛋白及血脂明显升高(P＜0. 05),而与肥胖组相比,利拉鲁肽组小鼠的上述指标均明显下降(P＜0. 05).与正常对照组相比,肥胖组小鼠肾脏SIRT-1、P-AMPK和LC3B均明显下降,P62累积增加,与肥胖组相比,利拉鲁肽组SIRT-1、P-AMPK和LC3B均明显升高,P62累积减少( P＜0. 05).结论 利拉鲁肽能减轻高脂诱导的肥胖相关性肾病小鼠的尿微量白蛋白,改善肾小球肥大、局灶节段性硬化及系膜基质增多的病变程度,机制可能通过诱导ORG小鼠的自噬发挥作用.%Objective To evaluate the effect of the glucagon-like peptide 1 ( GLP-1) receptor agonist liraglutide on obesity-related glomerulopathy ( ORG) in mice and its relationship with autophagy pathway SIRT-1/AMPK. Meth-ods Thirty-four male mice were randomly divided into normal control group(n=12) and hyperlipidemia group (n=22). The high-fat group was randomly divided into GLP-1 receptor agonist group (liraglutide group) and high-fat control group. After intervention for 12 weeks, renal pathological staining, serological and urinalysis were per-formed. Western blot was used to detect the expression of autophagy pathway protein in kidney tissues. Data were analyzed by means of homogeneity of variance. Results Compared with the normal control group, obesity group mice glomerular hypertrophy, mesangial matrix increased significantly, and accompanied by focal stage sclerosis. Compared with obesity group, liraglutide group mice kidney lesions significantly reduced. Compared with the normal control group, body weight, wet weight of right kidney and urine microalbumin and blood lipids in obesity group were significantly increased ( P＜0. 05) . Compared with obesity group, the above indicators of liraglutide group were significantly decreased (P＜0. 05). Compared with the normal control group, the obesity group SIRT-1, P-AMPK and LC3B were significantly decreased, P62 cumulative increased. Compared with obesity group, liraglutide group SIRT-1, P-AMPK and LC3B were significantly increased, P62 cumulative decreased. Conclusion Liraglu-tide can reduce urine microalbumin and improve the degree of glomerular hypertrophy, focal stage sclerosis and me-sangial matrix in high fat-induced obesity-related nephropathy mice, and the mechanism underlying may contribute to induction of autophagy in ORG mice.
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