Effect of sitagliptin on cardiomyocyte pyroptosis induced by type 2 diabe-tes mellitus and underlying mechanism
10.3969/j.issn.1000-4718.2018.06.002
- VernacularTitle:西格列汀对2型糖尿病大鼠心肌细胞焦亡的影响及其可能机制
- Author:
Jie XU
1
;
Ling YANG
;
Meng ZHANG
;
Min-Hang ZHU
;
Fen XIE
;
Xiao-Xia JIN
;
Qiong YUAN
;
Qian-Yi ZHOU
Author Information
1. 武汉科技大学医学院新药创制研究所
- Keywords:
Type 2 diabetes mellitus;
Diabetic cardiomyopathy;
Sitagliptin;
Pyroptosis;
SIRT3/NLRP3 sig-naling pathway
- From:
Chinese Journal of Pathophysiology
2018;34(6):969-974
- CountryChina
- Language:Chinese
-
Abstract:
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-SULTS:Compared 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.
