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2017年第10期
低中剂量饮酒通过抑制TNF-αFADDp53依赖的心肌细胞凋亡及4-HNE蓄积减少心肌缺血再灌注损伤
Low-to-Moderate Alcohol Consumption Attenuates Ischemia/Reperfusion Injury via Reduction of TNF- α/FADD/p53-dependent Apoptosis and 4-HNE Accumulation
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DOI:
作者:
韩莎莎,王振军,申程,王鹏,杨志寅, 孙爱军
HAN Shasha, WANG Zhenjun, SHEN Cheng, WANG Peng,YANG Zhiying,SUN Aijun
作者单位:
韩莎莎:山东大学医学院 济南 250012,复旦大学附属中山医院上海市心血管病研究所 王振军:开封市中心医院心内科 申程、王鹏:复旦大学附属中山医院上海市心血管病研究所 杨志寅:山东省济宁医学院行为医学研究所 孙爱军:复旦大学附属中山医院上海市心血管病研究所;复旦大学生物医学研究院
HAN Shasha:Department of Cardiology, School of Medicine, Shandong University ;Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University WANG Zhenjun:Department of Cardiology, Kaifeng Central Hospital SHEN Cheng, WANG Peng:Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University YANG Zhiying:Institute of Behavioral Medicine, Jining Medical College SUN Aijun;Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University;Institute of Biomedical Science, Fudan University
关键词:
低中剂量饮酒;缺血再灌注;心肌保护;凋亡;4-HNE
Low-to-moderate alcohol consumption; Ischemia/Reperfusion; Cardioprotection; Apoptosis; 4-HNE
摘要:
【摘要】目的 观察低中剂量饮酒对小鼠基础心功能、缺血再灌注损伤的影响及其机制探索。方法 20只雄性成年C57BL/6小鼠随机分为对照组和实验组。对照组给予正常饮水,实验组给予低中剂量梯度酒精(2.5%,5%,10%,18%)。6周后心脏超声检测心功能,H&E、Masson染色分析心肌病理学改变,离体心脏缺血再灌注(缺血30min再灌注40min)后利用TTC染色比较两组心梗面积,Western blot分析蛋白表达变化。结果 两组小鼠心功能正常(P值均>0.05),H&E及Masson染色结果显示两组心肌组织均无病理学改变(P值均>0.05),但实验组可明显减少心脏缺血再灌注的梗死面积(P<0.05)。此外,与对照组相比,实验组的TNF-α、FADD、p53及4-HNE的表达均显著下降(P值均<0.05)。结论 基础状态下低中剂量饮酒可能通过抑制TNF-α/FADD/p53信号通路减少心肌细胞凋亡及减轻毒性物质4-HNE蓄积抵抗缺血再灌注损伤。
【Abstract】 Objective To investigate the effect of low-to-moderate alcohol consumption on cardiac function and ischemia/reperfusion (I/R) injury,then to reveal the underlying mechanisms. Methods Twenty adult male C57BL/6 mice were randomly divided into control group (CON) feeding with water and low-to-moderate alcohol consumption group (EtOH) feeding with incremental v/v alcohol (2.5%, 5%, 10%, and 18%). Cardiac function was measured by echocardiography 6 weeks post water or alcohol consumption. The mice were subjected to Langendorff I/R model (30 min ischemia followed by 40min of reperfusion) and the infarct size was evaluated by TTC staining. Heart tissues were cut and stained with hematoxylin and eosin (H&E) and Masson, while the expressions of TNF-a, FADD, p53 and 4-HNE were examined by Western blot. Results Cardiac function of the two groups were similar. Analysis of H&E and Masson images did also not show any changes in arrangements, cross-sectional areas and collagen deposition between the two groups. Compared to the CON group, low-to-moderate alcohol consumption significantly decreased the ratio of infarct size and the changes were related to downregulated expressions of TNF-a, FADD, p53 and 4-HNE. Conclusion Low-to-moderate alcohol consumption attenuates I/R injury possibly by decreasing TNF-α/FADD/p53-dependent apoptosis and 4-HNE accumulation.
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