Ying-Wen Zhang1, Xiuping Wang2, Xiaodan Ren2, Manling Zhang2. 1. Department of Chinese with Western Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China. Electronic address: hhao3838@sina.com. 2. Department of Chinese with Western Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
Abstract
AIMS: To testing whether endoplasmic reticulum (ER) stress contributes to the development of diabetic nephropathy. Investigated the effect of gliclazide, an oral antihyperglycemic agent, in a rat model of diabetic nephropathy and the underlying mechanism related to the ER stress response. METHODS: Sixty SD rats were divided into six groups. Diabetic nephropathy was induced in 30 rats with a streptozotocin (STZ) injection and high fat diet, which were then treated with saline, gliclazide or 4-PBA. 20 rats were treated with Tunicamycin (TM) one-time intraperitoneal injection, following treated with saline or gliclazide. Blood glucose, kidney index and function were evaluated. Light and transmission electron microscopy (TEM) were used to observe kidney histological changes. Quantitative real-time PCR and western blot were performed to access the mRNA and protein levels of glucose-regulated protein 78 (GRP78) and spliced X-box binding protein 1 (sXBP1) in glomeruli. RESULT: STZ-induced diabetic rats evidenced nephropathy by higher serum creatinine (sCr), blood urea nitrogen (BUN), microalbuminuria (MAU), and kidney index. Histological examination and TEM assay showed abnormal renal structures including thick glomerular basement membrane and mesangial cell expansion. The same changes were found in TM-treated rats. Gliclazide-treated had similar kidney index, but lower glucose levels, sCr, BUN, and MAU, compared with both saline and 4-PBA-treated diabetic rats or saline-treated TM rats. Synchronize with significantly lower Grp78 and sXbp1 mRNA and protein levels. CONCLUSION: Diabetes-induced nephropathy is associated with ER stress. Gliclazide treatment lessens diabetic nephropathy, probably partially by suppressing the GRP78- and sXBP1-mediated ER response.
AIMS: To testing whether endoplasmic reticulum (ER) stress contributes to the development of diabetic nephropathy. Investigated the effect of gliclazide, an oral antihyperglycemic agent, in a rat model of diabetic nephropathy and the underlying mechanism related to the ER stress response. METHODS: Sixty SD rats were divided into six groups. Diabetic nephropathy was induced in 30 rats with a streptozotocin (STZ) injection and high fat diet, which were then treated with saline, gliclazide or 4-PBA. 20 rats were treated with Tunicamycin (TM) one-time intraperitoneal injection, following treated with saline or gliclazide. Blood glucose, kidney index and function were evaluated. Light and transmission electron microscopy (TEM) were used to observe kidney histological changes. Quantitative real-time PCR and western blot were performed to access the mRNA and protein levels of glucose-regulated protein 78 (GRP78) and spliced X-box binding protein 1 (sXBP1) in glomeruli. RESULT: STZ-induced diabeticrats evidenced nephropathy by higher serum creatinine (sCr), blood ureanitrogen (BUN), microalbuminuria (MAU), and kidney index. Histological examination and TEM assay showed abnormal renal structures including thick glomerular basement membrane and mesangial cell expansion. The same changes were found in TM-treated rats. Gliclazide-treated had similar kidney index, but lower glucose levels, sCr, BUN, and MAU, compared with both saline and 4-PBA-treated diabeticrats or saline-treated TMrats. Synchronize with significantly lower Grp78 and sXbp1 mRNA and protein levels. CONCLUSION:Diabetes-induced nephropathy is associated with ER stress. Gliclazide treatment lessens diabetic nephropathy, probably partially by suppressing the GRP78- and sXBP1-mediated ER response.
Authors: George J Dugbartey; Quinsker L Wonje; Karl K Alornyo; Louis Robertson; Ismaila Adams; Vincent Boima; Samuel D Mensah Journal: Front Pharmacol Date: 2022-03-21 Impact factor: 5.810