低剂量乙醇干预减轻糖尿病大鼠心肌纤维化的机制探讨

中国临床药理学与治疗学 ›› 2015, Vol. 20 ›› Issue (4): 379-383.

低剂量乙醇干预减轻糖尿病大鼠心肌纤维化的机制探讨

于影, 张冠军, 宗巧凤, 王晓梅, 李正红, 高琴

蚌埠医学院生理学教研室,蚌埠 233030,安徽

收稿日期:2014-11-10 修回日期:2015-03-27 发布日期:2015-05-07
通讯作者: 高琴,女,博士,副教授,研究方向:心血管生理学。Tel: 0552-3175268 E-mail: bbmcgq@126.com
作者简介:于影,女,硕士,讲师,研究方向:心血管生理学。Tel: 15056154653 E-mail: yuying2011@126.com
基金资助:
国家自然科学基金(81000074);安徽省自然科学基金(1508085QH150,1508085MH169);蚌埠医学院研究生科研创新计划项目(Byycxz1303)

Mechanism investigation of low dose ethanol intervention on myocardial fibrosis in diabetic rats

YU Ying, ZHANG Guan-jun, ZONG Qiao-feng, WANG Xiao-mei, LI Zhen-hong, GAO Qin

Department of Physiology, Bengbu Medical College, Bengbu 233030, Anhui, China

Received:2014-11-10 Revised:2015-03-27 Published:2015-05-07

摘要/Abstract

摘要： 目的: 观察低剂量乙醇干预对糖尿病大鼠心肌纤维化的影响,并初步探讨其机制。方法: 雄性SD大鼠分成正常对照组(Con),糖尿病4周组(DM 4w),糖尿病8周组(DM 8w)和乙醇+糖尿病8周组(EtOH+DM 8w)。造模8周后,检测血流动力学指标、心体比、心肌羟脯氨酸(Hp)含量,Masson染色测量胶原容积分数(CVF),Real-time PCR测定乙醛脱氢酶2(ALDH2)mRNA改变,Western blot测定p-JNK和JNK蛋白表达。结果: 与Con组大鼠相比,DM 4w组各项指标无明显改变;随病程延长,DM 8w组平均动脉压(MAP)和心率(HR)降低,心体比、Hp含量及CVF增高;ALDH2 mRNA表达下降,p-JNK/JNK增加(P<0.05)。与DM 8w组大鼠相比,EtOH+DM 8w组上述指标均有改善(P<0.05)。结论: 低剂量乙醇可能通过增高ALDH2表达、抑制JNK表达,改善糖尿病大鼠心肌纤维化损伤。

关键词: 糖尿病, 心肌纤维化, 乙醛脱氢酶2, JNK, 乙醇

Abstract: AIM: To study the effects of low dose ethanol intervention on myocardial fibrosis in diabetic rats and analyze its underlying mechanism.METHODS: Male SD rats were randomly divided into four groups: normal control group (Con), diabetes at 4th week group (DM 4w), diabetes at 8th week group (DM 8w) and ethanol + diabetes at 8th week group (EtOH+DM 8w). After 8 weeks, the hemodynamic parameters were recorded, heart weight/body weight ratio and hydroxyproline content in myocardium were measured. The changes of collagen morphology in myocardial tissue were observed with Masson staining, collagen volume fraction (CVF) was measured by image analysis. The expression of ALDH2 at mRNA level of myocardium were detected by Real-Time PCR analysis, and the protein expressions of p-JNK and JNK were detected by Western blot.RESULTS: In contrast with Con group, there were no differences about hemodynamic parameters in DM 4w group, but in DM 8w group, mean arterial pressure and heart rate were decreased, the ratio of heart weight/body weight, hydroxyproline content and CVF were markedly increased, ALDH2 mRNA expression was decreased, while the ratio of p-JNK/JNK were increased. Compared with DM 8W group, the above indexes were improved in EtOH+DM 8w group.CONCLUSION: Low dose ethanol ameliorated myocardial fibrosis in diabetic rats by up-regulating ALDH2 expression and down-regulating JNK expression.

Key words: diabetes, myocardial fibrosis, aldehyde dehydrogenase 2, JNK, ethanol

中图分类号:

于影, 张冠军, 宗巧凤, 王晓梅, 李正红, 高琴. 低剂量乙醇干预减轻糖尿病大鼠心肌纤维化的机制探讨[J]. 中国临床药理学与治疗学, 2015, 20(4): 379-383.

YU Ying, ZHANG Guan-jun, ZONG Qiao-feng, WANG Xiao-mei, LI Zhen-hong, GAO Qin. Mechanism investigation of low dose ethanol intervention on myocardial fibrosis in diabetic rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(4): 379-383.

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