摘要
目的:研究西格列汀(sitagliptin,SLT)对2型糖尿病大鼠心肌细胞焦亡的影响,并探讨其抑制糖尿病心肌病可能的作用机制。方法:建立2型糖尿病大鼠模型,并给予(3、10和30 mg/kg)和sirtuin(SIRT)家族抑制剂尼克酰胺(nicotinamide,NAM;500 mg/kg)灌胃4周。检测空腹血糖,采用免疫组织化学法和Western blot法检测心肌组织中相关蛋白表达。结果:与正常对照组相比,糖尿病大鼠心肌组织细胞SIRT3表达下调,而NLRP3表达上调(P<0.05),糖尿病大鼠心肌组织发生焦亡的细胞明显增多。灌胃SLT能剂量依赖性地抑制糖尿病大鼠心肌细胞焦亡的发生,并上调SIRT3的表达,下调NLRP3蛋白表达(P<0.05);SIRT3非特异性抑制剂NAM(500 mg/kg)能逆转SLT的心脏保护作用,与正常对照组相比,单独给予NAM(500 mg/kg)对正常大鼠心肌细胞SIRT3表达无明显作用,但NLRP3表达上调(P<0.05),心肌组织发生焦亡的细胞增多。结论:SLT能抑制糖尿病诱导的心肌细胞焦亡,其作用机制可能涉及SIRT3/NLRP3信号途径。
AIM： To explore the effect of sitagliptin（ SLT） on cardiomyocyte pyroptosis induced by type 2 diabetes 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 glucose was measured,and the tissue proteins were determined by the methods of Western blot and immunochemistry. RESULTS： 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 cardiomyocytes,downregulated the expression of NLRP3,and upregulated the expression of SIRT3 in a dose-dependent manner（ 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 pyroptosis of cardiomyocytes induced by diabetes,and the mechanism is related to the SIRT3/NLRP3 signaling pathway.
作者
徐洁
杨羚
张萌
朱敏航
谢芬
金晓霞
袁琼
周乾毅
XU Jie;YANG Ling;ZHANG Meng;ZHU Min-hang;XIE Fen;JIN Xiao-xia;YUAN Qiong;ZHOU Qian-yi(New Drug Innovation Institute,School of Medicine,Wuhan University of Science and Technology,Hubei Provincial Key La boratory of Occupational Hazard Identification and Control,Wuhan 430065,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2018年第6期969-974,共6页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81770377)
湖北省大学生创新创业训练计划(No.201510488045)
