Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, No. 149, Dalian Road, Huichuan, Zunyi, 563000, Guizhou, China.
Clin Exp Nephrol. 2024 Oct;28(10):1051-1061. doi: 10.1007/s10157-024-02516-4. Epub 2024 May 23.
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.
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.
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.
OAGB improved renal damage and fibrosis and lipids accumulation in DN rats by GLP-1-mediated Sirt1/AMPK/PGC1α pathway.
糖尿病肾病（DN）是糖尿病的一种并发症，是终末期肾病的主要原因。减重手术可缓解糖尿病及其并发症。一种吻合口胃旁路术（OAGB）是一种流行的减重手术，通过调节胰高血糖素样肽-1（GLP-1）水平来改善糖尿病及其并发症。同时，GLP-1 可减轻高脂饮食诱导肥胖大鼠的肾损伤。然而，OAGB 对 DN 患者的肾损伤的影响仍不确定。
通过高脂饮食喂养和链脲佐菌素（STZ）注射建立大鼠糖尿病模型。通过体重和肾脏重量及血糖监测、口服葡萄糖耐量试验（OGTT）、酶联免疫吸附试验（ELISA）、生化检测、组织病理学分析和 Western blot 分析研究 OAGB 在 DN 大鼠中的作用和机制。
OAGB 手术逆转了糖尿病大鼠体重和葡萄糖耐量指标的增加。此外，OAGB 手术中和了 DN 引起的平均肾脏重量、肾脏重量/体重比以及肾脏损伤指标的增加，同时减轻了肾小球肥大、减轻了系膜扩张并减少了肾小管和肾小球周胶原沉积。此外，OAGB 手术减少了 DN 引起的肾脏甘油三酯和胆固醇含量，同时调节了脂肪酸相关蛋白的表达。机制上，OAGB 给药挽救了 GLP-1 介导的 Sirt1/AMPK/PGC1α 通路介导的 DN 大鼠中的表达。GLP-1 受体的药理学阻断反转了 OAGB 手术对 DN 大鼠体重、葡萄糖耐量、肾脏组织损伤、纤维化和脂肪堆积的影响。
OAGB 通过 GLP-1 介导的 Sirt1/AMPK/PGC1α 通路改善了 DN 大鼠的肾脏损伤和纤维化以及脂肪堆积。
