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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

徐洁 杨羚 张萌 朱敏航 谢芬 金晓霞 袁琼 周乾毅

中国病理生理杂志2018,Vol.34Issue(6):969-974,6.
中国病理生理杂志2018,Vol.34Issue(6):969-974,6.DOI:10.3969/j.issn.1000-4718.2018.06.002

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

Effect of sitagliptin on cardiomyocyte pyroptosis induced by type 2 diabe-tes mellitus and underlying mechanism

徐洁 1杨羚 1张萌 1朱敏航 1谢芬 1金晓霞 1袁琼 1周乾毅1

作者信息

  • 1. 武汉科技大学医学院新药创制研究所,职业危害识别与控制湖北省重点实验室,湖北 武汉430065
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摘要

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.

关键词

2型糖尿病/糖尿病心肌病/西格列汀/细胞焦亡/SIRT3/NLRP3信号通路

Key words

Type 2 diabetes mellitus/Diabetic cardiomyopathy/Sitagliptin/Pyroptosis/SIRT3/NLRP3 sig-naling pathway

分类

医药卫生

引用本文复制引用

徐洁,杨羚,张萌,朱敏航,谢芬,金晓霞,袁琼,周乾毅..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[J].中国病理生理杂志,2018,34(6):969-974,6.

基金项目

国家自然科学基金资助项目(No.81770377) (No.81770377)

湖北省大学生创新创业训练计划(No.201510488045) (No.201510488045)

中国病理生理杂志

OA北大核心CSCDCSTPCD

1000-4718

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