背景:糖尿病肾病(DN),糖尿病的并发症,是导致终末期肾病的主要原因.减重手术对缓解糖尿病和糖尿病相关并发症的作用。一次吻合胃旁路术(OAGB),流行的减肥手术之一,可以通过调节胰高血糖素样肽-1(GLP-1)水平改善糖尿病及其并发症。同时,GLP-1可减轻高脂饮食诱导的肥胖大鼠的肾损伤。然而,OAGB对DN肾损伤的影响尚不确定。
方法:通过HFD喂养和STZ注射诱导大鼠糖尿病模型。OAGB在DN大鼠中的作用和机制,通过体重和肾脏的体重和血糖监测,口服葡萄糖耐量试验(OGTT),酶联免疫吸附测定(ELISA),生物化学检测,组织病理学分析,和蛋白质印迹分析。
结果:OAGB手术逆转了糖尿病大鼠体重和糖耐量指标的增加。此外,OAGB手术中和了DN诱导的平均肾脏重量,肾脏重量/体重,和肾损伤指数伴随肾小球肥大减少,肾小球膜扩张减轻,肾小管和肾小球周围胶原沉积减少。此外,OAGB的引入通过调节脂肪酸相关蛋白的表达降低了DN诱导的肾甘油三酯和肾胆固醇。机械上,OAGB给药挽救了DN诱导的GLP-1介导的Sirt1/AMPK/PGC1α途径的表达。GLP-1受体的药物阻断逆转了OAGB手术对体重的影响,葡萄糖耐量,肾组织损伤,DN大鼠的纤维化和脂质积累。
结论:OAGB通过GLP-1介导的Sirt1/AMPK/PGC1α途径改善DN大鼠肾损伤、纤维化和脂质蓄积。
BACKGROUND: Diabetic nephropathy (DN), a complication of diabetes, is the most leading cause of end-stage renal disease. Bariatric surgery functions on the remission of diabetes and diabetes-related complications. One anastomosis gastric bypass (OAGB), one of popular bariatric surgery, can improve diabetes and its complications by regulating the glucagon-like peptide-1 (GLP-1) level. Meanwhile, GLP-1 can alleviate renal damage in high-fat-diet-induced obese rats. However, the effect of OAGB on renal injury remains uncertain in DN.
METHODS: A diabetes model was elicited in rats via HFD feeding and STZ injection. The role and mechanism of OAGB were addressed in DN rats by the body and kidney weight and blood glucose supervision, oral glucose tolerance test (OGTT), enzyme-linked immunosorbent assay (ELISA), biochemistry detection, histopathological analysis, and western blot assays.
RESULTS: OAGB surgery reversed the increase in body weight and glucose tolerance indicators in diabetes rats. Also, OAGB operation neutralized the DN-induced average kidney weight, kidney weight/body weight, and renal injury indexes accompanied with reduced glomerular hypertrophy, alleviated mesangial dilation and decreased tubular and periglomerular collagen deposition. In addition, OAGB introduction reduced the DN-induced renal triglyceride and renal cholesterol with the regulation of fatty acids-related proteins expression. Mechanically, OAGB administration rescued the DN-induced expression of Sirt1/AMPK/PGC1α pathway mediated by GLP-1. Pharmacological block of GLP-1 receptor inverted the effect of OAGB operation on body weight, glucose tolerance, renal tissue damage, and fibrosis and lipids accumulation in DN rats.
CONCLUSIONS: OAGB improved renal damage and fibrosis and lipids accumulation in DN rats by GLP-1-mediated Sirt1/AMPK/PGC1α pathway.