培哚普利通过调节Akt-FoxO1通路保护糖尿病性心肌病大鼠心功能损伤

doi:10.6040/j.issn.1671-7554.0.2016.1152

摘要/Abstract

摘要： 目的探讨培哚普利对糖尿病性心肌病(DCM)大鼠心功能损伤的影响及其潜在的作用机制。方法 40只8周龄(100~120 g)雄性Sprague-Dawley大鼠随机分为对照组(n=10)、DCM组(n=15)和DCM+培哚普利组(n=15)。对照组给予普通饮食饲养,其他两组制备糖尿病性心肌病大鼠模型。模型建立成功后,DCM组给予高脂饮食饲养和生理盐水灌胃,DCM+培哚普利组给予高脂饮食饲养和培哚普利灌胃4 mg/(kg·d)。观察培哚普利对糖尿病性心肌病大鼠心功能、心肌细胞凋亡和心肌纤维化的影响,以及其对Akt-FoxO1信号通路的影响。结果 DCM组较对照组心功能降低,心肌细胞凋亡和心肌纤维化程度增加,Akt的磷酸化水平降低,FoxO1的蛋白表达升高,两组差异有统计学意义(P<0.05);DCM+培哚普利组较DCM组心功能损伤减轻,并影响Akt-FoxO1的表达水平,两组差异有统计学意义(P<0.05)。结论培哚普利通过调节Akt-FoxO1信号通路抑制DCM大鼠的心肌细胞凋亡和心肌纤维化,保护DCM大鼠的心功能损伤。

关键词: 糖尿病性心肌病, 培哚普利, 心功能, 凋亡, 纤维化

Abstract: Objective To investigate the role and potential mechanism of perindopril on myocardial dysfunction in DCM(diabetic cardiomyopathy). Methods A total of 40 male Sprague-Dawley rats(100-120 g)were divided into 3 groups: control(n=10), DCM group(n=15)and DCM+perindopril group(n=15). The control group was fed with basal diet, while the DCM group and DCM+perindopril group were established as diabetic models. After the models were successfully established, the DCM group received intragastric normal saline, and DCM+perindopril group received intragastric perindopril 4 mg/(kg·d). The effect of perindopril on the rats cardiac function, myocardial apoptosis and fibrosis were observed. The protein expressions of p-Akt and p-FoxO1 were examined withWestern blotting. Results Compared with the control group, the DCM group exhibited severe left ventricular dysfunction, myocardial apoptosis and fibrosis, significantly increased p-FoxO1 expressio and decreased p-Akt protein expression(P<0.05). Compared with the DCM group, the DCM+perindopril group had better cardiac function and lower p-Akt protein expression(P<0.05). Conclusion Perindopril protects cardiac function by inhibiting myocardial apoptosis and fibrosis in diabetic rat svia Akt-FoxO1 pathway.

Key words: Perindopril, Cardiac function, Apoptosis, Fibrosis, Diabetic cardiomyopathy

中图分类号:

R587.2

巩璐伟,周丽珍,苏国海. 培哚普利通过调节Akt-FoxO1通路保护糖尿病性心肌病大鼠心功能损伤[J]. 山东大学学报（医学版）, 2017, 55(10): 65-70.

GONG Luwei, ZHOU Lizhen, SU Guohai. Perindopril ameliorates cardiac dysfunction via Akt-FoxO1 pathway in diabetic cardiomyopathy[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(10): 65-70.

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