Effect of Dapagliflozin on kidney injury in diabetic nephropathy mice through Caspase-1 mediated pyroptosis
WANG Ying1 YIN Doudou1 CHAO Nan2
1.The First Department of Internal Medicine, Changzhou Medical District, the 904th Hospital of the Joint Logistics Support Force of Chinese People’s Liberation Army, Jiangsu Province, Changzhou 213000, China;
2.Department of Pharmacy, Changzhou Medical District, the 904th Hospital of the Joint Logistics Support Force of Chinese People’s Liberation Army, Jiangsu Province, Changzhou 213000, China
Abstract：Objective To investigate the effect of Dapagliflozin (DAP) on kidney injury in diabetic nephropathy (DN) mice based on the pyrocytosis mediated by cysteine aspartic acid specific protease-1(Caspase-1) pathway. Methods Thirty SPF grade C57BL/6 male mice, aged eight weeks and weighing 17-25 g, were divided into control group, model group, and DAP group with ten mice in each group according to random number table method. DN model was established in model group and DAP group, and ordinary diet was given to control group. DAP group was given 1 mg/ (kg·d) DAP by intragastric administration, while control group and model group were given the same amount of normal saline by intragastric administration for consecutive four weeks. After drug intervention, the general conditions, serum creatinine, 24 h urinary protein, and serum interleuking-18 (IL-18) levels of each group were compared. Pathological changes of kidney were observed. The expression of Caspase-1 pathway related proteins in mouse kidney was compared. Results Compared with the control group, the model group was listless, less active, occasionally shivering, urine volume was increased significantly, and thinner. Compared with model group, DAP group showed polydipsia and hyperbiosis, and the urine volume was not obvious increased and the activity was normal. Compared with control group, 24 h urinary protein, serum creatinine, serum IL-18 levels and NLR family pyrin domain containing 3 (NLRP3), Caspase-1, GSDMD, and IL-18 protein levels in model group were significantly increased (P＜0.05). Compared with model group, 24 h urinary protein, serum creatinine and serum IL-18 levels, NLRP3, Caspase-1, GSDMD, and IL-18 protein levels in DAP group were significantly decreased (P＜0.05). Conclusion DAP may protect kidney by inhibiting NLRP3/Caspase-1 signaling pathway to activate and inhibit pyrodeath.
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