利拉鲁肽激活糖尿病大鼠肾脏内皮源性一氧化氮合酶活性降低尿白蛋白排泄的研究

Liraglutide reduces urinary albumin excretion by activating endothelial nitric oxide synthase of kidney in diabetic rats

目的探讨利拉鲁肽对糖尿病大鼠24hUAlb排泄的影响及机制。方法将30只大鼠分为正常对照(NC)组、糖尿病(DM)组和利拉鲁肽(DM+L)组。检测各组给药前后血肌酐(Scr)、BUN和24hUAlb。HE、PAS染色观察肾脏形态学改变;Western blot检测肾脏GLP-1受体(GLP-1R)、内皮源性一氧化氮合酶(eNOS)、p-eNOS表达;ELISA检测eNOS活性。结果与NC组相比,DM组Scr、BUN、24hUAlb升高,肾脏eNOS表达比较差异无统计学意义,GLP-1R、p-eNOS表达及eNOS活性降低(P<0.01)。与DM组相比,DM+L组Scr、BUN、24hUAlb降低,肾脏GLP-1R、p-eNOS表达及eNOS活性升高(P<0.05或P<0.01)。结论利拉鲁肽可上调糖尿病大鼠肾脏GLP-1R表达,提高肾小球血管内皮细胞eNOS活性,减少糖尿病大鼠UAlb排泄。

Objective To explore the effects of liraglutide on 24 hUAlb excretion in diabetic rats and its potential mechanism. Methods 30 rats were divided into normal control(NC),diabetes(DM)and liraglutide treated DM(DM+L)group.Serum creatinine(Scr),BUN and 24 hUAlb were measured before and after treatment.Renal morphological changes were evaluated by HE and PAS staining.Protein expressions of GLP-1receptor(GLP-1R),endothelial nitric oxide synthase(eNOS),and p-eNOS were detected by Western blot.The eNOS activity was determined by ELISA. Results Compared to NC group,DM group and DM+L group showed that Scr,BUN,24 hUAlb excretion were significantly increased and that specimen of renal biopsy showed inflammatory cells infiltration,fibrosis and even glomerular sclerosis.There were no significant differences in eNOS expression between two groups,however the expression of GLP-1R,p-eNOS and eNOS activity were significantly decreased(P<0.01).Compared with DM group,DM+L group showed that Scr,BUN and 24 hUAlb excretion were significantly decreased,and that the expression of GLP-1R,p-eNOS and eNOS activity were significantly increased(P<0.05 or P<0.01). Conclusion Liraglutide could reduce urinary albumin excretion through upregulating the expression of GLP-1Rand then activating eNOS in kidney.