Rui Xin1, Xuhong Sun1, Ziying Wang2, Wendan Yuan1, Weidong Jiang3, Lin Wang3, Yanxiao Xiang4, Hongqin Zhang1, Xiaoyan Li1, Yun Hou1, Wangnan Sun1, Pengchao Du5. 1. School of Basic Medical Sciences, Binzhou Medical University, Yantai, Shandong, China. 2. Department of Pharmacology, School of Basic Medical Science, Shandong University, Jinan, China. 3. Department of Gerontology, the Second Hospital of Shandong University, Jinan, Shandong, China. 4. Qilu Hospital, Shandong University, Jinan, Shandong, China. 5. School of Basic Medical Sciences, Binzhou Medical University, Yantai, Shandong, China. Electronic address: pengchaodu@163.com.
Abstract
AIMS: In this animal study, we tried to test the hypothesis that apocynin could play an anti-inflammation role by inhibiting NLRP3/X-linked inhibitor of apoptosis protein (XIAP) signalling and have an effect on antifibrosis in rats with diabetic nephropathy. MAIN METHODS: Diabetic nephropathy rats were induced by tail-vein injection of streptozotocin at 60 mg/kg body weight in sodium citrate buffer (0.01 M, pH 4.5) with unrestricted access to food/water for 12 weeks, and rats with blood glucose levels above 18.0 mM were considered diabetic; the damage index for glomerular mesangial cells damage index was calculated by morphological examinations; protein and mRNA changes were analysed by western blotting immunohistochemistry and real-time quantitative polymerase chain reaction; interstitial fibrosis was assessed and scored using Masson's staining. KEY FINDINGS: In rats with diabetic nephropathy, apocynin (1) reduced renal injury and improved renal function; (2) downregulated the expression of NLRP3 in renal cortex; (3) downregulated the expression of XIAP in renal cortex; and (4) attenuated renal fibrosis. SIGNIFICANCE: As an inhibitor of reactive oxygen species (ROS), apocynin could downregulate the expression of NLRP3 and XIAP, and alleviate renal fibrosis, which meant not only that ROS was one type of ligands of NLRP3, but also that ROS mechanism and NLRP3 activation might be therapeutic targets in the treatment of diabetic nephropathy in the future.
AIMS: In this animal study, we tried to test the hypothesis that apocynin could play an anti-inflammation role by inhibiting NLRP3/X-linked inhibitor of apoptosis protein (XIAP) signalling and have an effect on antifibrosis in rats with diabetic nephropathy. MAIN METHODS:Diabetic nephropathyrats were induced by tail-vein injection of streptozotocin at 60 mg/kg body weight in sodium citrate buffer (0.01 M, pH 4.5) with unrestricted access to food/water for 12 weeks, and rats with blood glucose levels above 18.0 mM were considered diabetic; the damage index for glomerular mesangial cells damage index was calculated by morphological examinations; protein and mRNA changes were analysed by western blotting immunohistochemistry and real-time quantitative polymerase chain reaction; interstitial fibrosis was assessed and scored using Masson's staining. KEY FINDINGS: In rats with diabetic nephropathy, apocynin (1) reduced renal injury and improved renal function; (2) downregulated the expression of NLRP3 in renal cortex; (3) downregulated the expression of XIAP in renal cortex; and (4) attenuated renal fibrosis. SIGNIFICANCE: As an inhibitor of reactive oxygen species (ROS), apocynin could downregulate the expression of NLRP3 and XIAP, and alleviate renal fibrosis, which meant not only that ROS was one type of ligands of NLRP3, but also that ROS mechanism and NLRP3 activation might be therapeutic targets in the treatment of diabetic nephropathy in the future.
Authors: F Timóteo-Ferreira; S Mendes; N A Rocha; L Matos; A R Rodrigues; H Almeida; E Silva Journal: Oxid Med Cell Longev Date: 2019-10-20 Impact factor: 6.543