慢性间歇性低压低氧预处理可减轻大鼠放射性心脏损伤

doi:10.3760/cma.j.issn.1004-4221.2017.02.020

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摘要目的研究慢性间歇性低压低氧(CIHH)对急性期放射性心脏损伤影响及作用机制。方法成年雄性SD大鼠48只随机分为空白对照组、CIHH组、照射组和CIHH+照射组。CIHH处理为动物在接受照射前置于低压氧仓预处理。记录左心室功能,测定心肌梗死面积。Masson染色后计算心肌胶原容积分数(CVF),ELISA法检测心肌组织总超氧化物歧化酶(T-SOD)活力和丙二醛(MDA)含量。蛋白印迹法检测纤维化标志物Ⅰ型胶原(COL-1)、内质网应激相关蛋白GRP78和CHOP表达情况。差异检验采用双因素方差分析。结果 CIHH预处理后再照射大鼠左心室收缩及舒张功能有所改善,心肌梗死面积减小。CIHH+照射组较照射组CVF下降同时伴随COL-1表达水平降低(P<0.01,P<0.01)。CIHH+照射组T-SOD活力较照射组明显升高[(185.19±3.20) U/mgprot∶(156.61±4.60) U/mgprot,P<0.01],MDA浓度下降[(1.36±0.17) nmol/mgprot∶(2.36±0.21) nmol/mgprot,P<0.01]。CIHH+照射组与照射组比较内质网应激标志性蛋白GRP78和CHOP蛋白水平亦均降低(P<0.05,P<0.01)。结论 CIHH预处理在一定程度上能改善放射线引起的冠状动脉损伤,增强心脏对缺血再灌注损伤耐受性,减小缺血再灌注后心肌梗死面积,并减少小血管周围和心肌间质胶原沉积。CIHH可能通过抑制氧化应激、内质网应激及抑制心肌纤维化等对心肌起保护作用。

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	武亚晶
	王军
	王媛
	王升
	刘青
	王祎
	曹峰
	程云杰
	焦文鹏

关键词 ：慢性间歇性低压低氧, 放射性心脏损伤, Langendroff灌流, 内质网应激, 氧化应激

Abstract：Objective To study cardioprotective effects of pretreatment with chronic intermittent hypobaric hypoxia (CIHH) on acute radiation-induced heart damage, and to explore the potential mechanisms. Methods Forty-eight male adult Sprague-Dawley rats were randomly divided into control group, CIHH group, radiation group, and CIHH+radiation group. Pretreatment with CIHH was performed by placing rats in a hypobaric chamber before radiation. Left ventricular function was recorded and myocardial infarction area was determined. Collagen volume fraction (CVF) was calculated after Masson staining. The activity of total superoxide dismutase (T-SOD) and content of lipid peroxide malondialdehyde (MDA) were determined by enzyme linked immunosorbent assay. The expression levels of a marker of fibrosis, collagen type I (COL-1), and two markers of endoplasmic reticulum stress, GRP78 and CHOP, were analyzed by Western blot. Difference test using two factor analysis of variance. Results Compared with the radiation group, the CIHH+radiation group had improved left ventricular systolic and diastolic function and reduced myocardial infarction area;the CIHH+radiation group also had significantly reduced CVF, significantly lower expression of COL-1, significantly higher activity of T-SOD, significantly lower concentration of MDA, and significantly lower expression levels of GRP78 and CHOP (P<0.01,P<0.01;(185.19±3.20) vs. (156.61±4.60) U/mgprot, P<0.01;(1.36±0.17) vs. (2.36±0.21) nmol/mgprot, P<0.01;P<0.05;P<0.01). Conclusions Pretreatment with CIHH can to a certain degree reduce radiation-induced damage to the cardiac coronary artery, enhance cardiac tolerance to ischemia/reperfusion injury, reduce myocardial infarction area after ischemia/reperfusion, and improve collagen deposition in perivascular region and myocardial stroma. CIHH protects myocardium probably via inhibition of oxidative stress, endoplasmic reticulum stress, and myocardial fibrosis.

Key words： Chronic intermittent hypobaric hypoxia Radiation induced heart damage Langendorff perfusion Endoplasmic reticulum stress Oxidative stress

收稿日期: 2016-07-11

通讯作者: 王军,Email:wangjunzr@163.com;王升,Email:wangsheng@hebmu.edu.cn

引用本文:

武亚晶,王军,王媛等. 慢性间歇性低压低氧预处理可减轻大鼠放射性心脏损伤[J]. 中华放射肿瘤学杂志, 2017, 26(2): 222-227.

Wu Yajing,Wang Jun,Wang Yuan et al. Pretreatment with chronic intermittent hypobaric hypoxia attenuates radiation-induced heart damage in rats[J]. Chinese Journal of Radiation Oncology, 2017, 26(2): 222-227.

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