Effects of liraglutide on expression of angiotension-Ⅱ type 1 and type 2 receptors in renal tissues of rats with diabetic nephropathy

Abstract:

Objective：To explore the effects of liraglutide on renal angiotension Ⅱ type 1 receptor（AT-1R） and angiotensionII type 2 receptor（AT-2R） of rats with type 2 diabetes. Methods：Forty adult male sprague-dawley rats were randomly separated into three groups：normal control group（NC），diabetic model group（DM） and liraglutide group（LR）. The rats of DM and LR group received in－traperitioneal injection of low dose of streptozotocin（STZ） after high fat and high glucose breeding to form an experimental model of type 2 diabetes. The rats of NC and LR group received liraglutide 100 ug/kg twice a day by hypodermic injection and the rats of DM group received injection of physiological saline. Twelve weeks after the build of type 2 diabetes model，the following indicators were assayed：（1）24 h urinary albumin excretion rate（UAER），serum creatinine（Scr） and blood urea nitrogen（BUN）；（2）body weight（BW），kidney weight（KW），KW/BW，mean glomerular volume（MGV） and fractional mesangial area（FMA）；（3）the changes of patho－logic feature of the kidney by periodic acid-silver methe-namine staining（PASM） and electron microscope；（4）the change of expres－sion of AT-1R and AT-2R in kidney of rats by immunohistchemistry and RT-PCR. Results：（1）Liraglutide can markedly suppress the augmentation of KW/BW，MGV，FMA，Scr，BUN and UAER as well as attenuate the renal pathologic lesions such as podocyte foot process fuse and glomerular basement membrane（GBM） thickening. （2）Liraglutide can up-regulate the expression of AT-2R in the kidney of diabetic rats meanwhile has no evident effect on the expression of AT-1R. Conclusion：Mechanism of reno-protection of li－raglutide may at least partly correlate with increased expression of AT-2R and change in balance of AT-1R/AT-2R of renal tis－sue.