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间歇性低压低氧方式对发育大鼠心脏缺血/再灌注损伤的影响

张浩, 杨长瑛, 王莹萍, 王昕, 崔芳, 周兆年, 张翼

河北医科大学生理学教研室.河北,石家庄 050017；中科院上海生命科学研究院.上海 200031

摘要

该研究旨在探讨两种不同形式的间歇性低压低氧(intermittent hypobaric hypoxia,IHH)对发育大鼠心脏缺血/再灌注损伤的影响。雄性Sprague--Dawley(SD)新生大鼠72只,随机分为三组:对照组、IHH 3000m组(IHH3000)、IHH5000m组(IHH5000)。低氧组大鼠出生后立即于低压氧舱分别接受28d、42d和56d(海拔5000m、每天6h;海拔3000m、每天5h)的低压低氧处理。应用Langendorff离体心脏灌流技术,给予心脏缺血(停灌30min)/再灌注(复灌60min)处理,分别在缺血前5min及复灌后1、5、10、20、30、60min记录心功能和冠状动脉流量变化,并测定乳酸脱氢酶(lactate dehydrogenase,LDH)活性。实验结束时测定心脏重量。结果显示:(1)IHH3000组大鼠体重增长与对照组无明显差异;IHH5000组大鼠体重增长明显慢于对照组及IHH3000组大鼠({sl P}<0.01)。(2)IHH3000组大鼠表现明显的心脏保护效应。与对照组相比较,在心脏停灌/再灌注60min时,心功能(LVDP、±LVdp/dt_(max))恢复增强({sl P}<0.05)、LDH活性降低({sl P}<0.05)、冠状动脉流量增多({sl P}<0.05);心脏重量与对照组大鼠无差异;IHH 42 d处理的大鼠心功能恢复明显好于IHH 28 d处理的大鼠({sl P}<0.05)。(3)IHH5000组大鼠表现出明显的心脏损伤效应,各项心功能指标(LVDP、±LVdp/dt_(max))的恢复均低于对照组({sl P}<0.05),复灌过程中LDH活性明显高于相应对照组({sl P}<0.05),右心室重量明显高于对照组大鼠({sl P}<0.05)。结果表明,适当的IHH增强发育大鼠心脏对缺血/再灌注损伤的抵抗能力;间歇性低氧方式是影响其心脏保护作用的重要因素。

关键词： 间歇性低氧; 大鼠; 心脏; 缺血/再灌注; 乳酸脱氢酶

Effects of different modes of intermittent hypobaric hypoxia on ischemia/reperfusion injury in developing rat hearts

Zhang Hao, Yang Changying, Wang Yingping, Wang Xin, Cui Fang, Zhou Zhaonian, Zhang Yi

Department of Physiology, Hebei Medical University.Shijiazhuang 050017,Hebei；China

Abstract

The aim of the present study was to explore the effects of two different modes of intermittent hypobaric hypoxia (IHH) on myocardial ischemia/reperfusion injury in developing rat hearts. Postnatal male sprague-Dawley rats (n=72) were divided randomly into 3 groups: intermittent hypoxia at 3 000 m (IHH3000) group, intermittent hypoxia at 5 000 m (IHH5000) group and control group.The isolated hearts were perfused in the Langendorff apparatus, undergoing 30 min of global ischemia and 60 min of reperfusion.Cardiac function, coronary flow and lactate dehydrogenase (LDH) activity were recorded at 5 min before ischemia and 1, 5, 10, 20, 30,60 min during reperfusion, respectively. The heart weight was measured at the end of the experiment. The results showed that: (1)There was no difference in body weight gaining between IHH3000 and control groups. The gain of body weight in IHH5000 group was much lower than that in IHH3000 and control groups (P＜0.01). (2) Compared with that in the control group, the recovery of cardiac function in IHH3000 group was enhanced at 60 min after ischemia/reperfusion, coronary flow was increased, and LDH activity was decreased (P＜0.05), meaning a cardioprotective effect occurred. There was no significant difference in heart weight between IHH3000and control groups. In addition, cardiac function restored better in IHH3000 group after 42 d of hypoxic exposure than that after 28 d of hypoxic exposure (P＜0.05). (3) Compared with that in the control group, the recovery of cardiac function in IHH5000 group was lower, coronary flow was decreased, and LDH activity was increased (P＜0.05). There was a hypertrophy in the right ventricle in IHH5000 group. All changes indicated definitely that a detrimental effect developed in IHH5000 group. The results suggest that proper IHH can protect developing rat hearts against ischemia/reperfusion injury while this effect could be affected by the modes of intermittent hypoxic exposure.

Key words: intermittent hypoxia;Rat;Heart;ischemia/reperfusion;lactate dehydrogenase

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引用本文：

张浩, 杨长瑛, 王莹萍, 王昕, 崔芳, 周兆年, 张翼. 间歇性低压低氧方式对发育大鼠心脏缺血/再灌注损伤的影响[J]. 生理学报 2007; 59 (5): 660-666.

Zhang Hao, Yang Changying, Wang Yingping, Wang Xin, Cui Fang, Zhou Zhaonian, Zhang Yi. Effects of different modes of intermittent hypobaric hypoxia on ischemia/reperfusion injury in developing rat hearts. Acta Physiol Sin 2007; 59 (5): 660-666 (in Chinese with English abstract).