Effect of sitagliptin on cardiomyocyte pyroptosis induced by type 2 diabe-tes mellitus and underlying mechanism / 中国病理生理杂志
Jie XU; Ling YANG; Meng ZHANG; Min-Hang ZHU; Fen XIE; Xiao-Xia JIN; Qiong YUAN; Qian-Yi ZHOU.
Chinese Journal of Pathophysiology
; (12): 969-974, 2018.
Artículo
en Zh
| WPRIM | ID: wpr-701225
AIM:
To explore the effect of sitagliptin (SLT) on cardiomyocyte pyroptosis induced by type 2 dia-betes mellitus (T2DM) and the underlying mechanism.METHODS:
The T2DM rat model was established by high-fat diet and intraperitoneal injection of streptozotocin (35 mg/kg). The model rats were treated with SLT at 3, 10 and 30 mg/kg and nicotinamide [NAM; an non-specific inhibitor of sirtuin (SIRT) family] at 500 mg/kg for 4 weeks. Fasting blood glu-cose was measured, and the tissue proteins were determined by the methods of Western blot and immunochemistry. RE-SULTSCompared with control group, the pyroptosis of cardiomyocytes and NLRP3 expression were significantly induced, while the protein level of SIRT3 was downregulated by T2DM (P<0.05). SLT inhibited the pyrpotosis of diabetic rat car-diomyocytes, downregulated the expression of NLRP3, and upregulated the expression of SIRT3 in a dose-dependent man-ner (P<0.05). All the function of SLT (30 mg/kg) was reversed by the treatment with NAM (500 mg/kg). Compared with control group, the pyroptosis of cardiomyocytes and NLRP3 expression were significantly induced, while the protein level of SIRT3 was not regulated by NAM (500 mg/kg).CONCLUSION:
SLT exerts the inhibitory effect on the pyropto-sis of cardiomyocytes induced by diabetes, and the mechanism is related to the SIRT3/NLRP3 signaling pathway.
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