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慢性间歇性低压低氧对成年和幼年大鼠缺血/再灌注心脏保护作用的比较
引用本文:马会杰,李茜,王福伟,王璐,马慧娟,史敏,张浩,张翼.慢性间歇性低压低氧对成年和幼年大鼠缺血/再灌注心脏保护作用的比较[J].中国药理学通报,2010,26(1).
作者姓名:马会杰  李茜  王福伟  王璐  马慧娟  史敏  张浩  张翼
作者单位:河北医科大学生理学教研室,河北,石家庄,050017
基金项目:国家自然科学基金资助项目,国家重点基础研究发展计划(973计划)资助项目,高等学校博士学科点专项科研基金资助,河北卫生厅医学科学研究重点课题 
摘    要:目的观察慢性间歇性低压低氧(CIHH)对成年和幼年大鼠心脏缺血/再灌注损伤的保护作用的异同点。方法♂成年和新生Sprague-Dawlay(SD)大鼠随机分为4组:对照28d组(CON28)、对照42d组(CON42)、CIHH处理28d组(CIHH28)和CIHH处理42d组(CIHH42)。间歇性低氧处理组动物于低压氧舱分别接受28d、42d模拟3000米海拔高度(PB=525mmHg,PO2=108.8mmHg)的低压低氧处理,每天5h。对照组动物除了不接受低氧处理外,其它处理均与间歇性低氧组动物相同。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,记录离体大鼠心脏在不同时期的心功能变化。心功能参数包括左室发展压(left ventricular developing pressure,LVDP)、左室压力最大变化速率(maximum changerate of LVDP,±LVdp/dtmax)、左室舒张末压(left ventricularend di-astolic pressure,LVEDP)、冠脉流量(coronary flow,CF)和心率(heartrate,HR)。结果①对成年大鼠,基础状态和缺血/再灌注状态下CIHH28d组各心功能参数与CON28d组相比差异均无统计学意义。CIHH42d组各心功能参数均好于CON42d组,表现为LVDP、LVEDP、±LVdp/dtmax和CF恢复均增加(P<0.05)。②对幼年大鼠,基础状态下,CIHH大鼠CF较对照大鼠明显增多,其余心功能参数与对照大鼠无差异。CIHH大鼠缺血/再灌注后心脏功能的恢复明显好于对照动物,表现为LVDP、LVEDP、±LVdp/dtmax和CF恢复均增加(P<0.05),且CIHH42d组比CIHH28d组心功能改善更明显。结论CIHH可增强成年和幼年大鼠抗心肌缺血/再灌注损伤的能力,具有明显的心脏保护作用,CIHH42d组保护作用更为明显;CIHH的心脏保护作用有明显的年龄差异,在幼年大鼠更易产生保护作用。

关 键 词:慢性间歇性低压低氧  成年大鼠  幼年大鼠  心脏  缺血/再灌注  心功能

Comparison of cardioprotection of chronic intermittent hypobaric hypoxia against ischemia/reperfusion injury between adult and young rats
MA Hui-jie,LI Qian,WANG Fu-wei,WANG Lu,MA Hui-juan,SHI Min,ZHANG Hao,ZHANG Yi.Comparison of cardioprotection of chronic intermittent hypobaric hypoxia against ischemia/reperfusion injury between adult and young rats[J].Chinese Pharmacological Bulletin,2010,26(1).
Authors:MA Hui-jie  LI Qian  WANG Fu-wei  WANG Lu  MA Hui-juan  SHI Min  ZHANG Hao  ZHANG Yi
Abstract:Aim To observe the cardioprotection of chronic intermittent hypobaric hypoxia (CIHH) against ischemia/reperfusion injury in adult and young rats.Methods Adult and postnatal male Sprague-Dawley rats were divided randomly into four groups:control 28-day group (CON28),control 42-day group (CON42), CIHH 28-day treatment group (CIHH28), and CIHH 42-day treatment group (CIHH42). CIHH animals with maternal rats were put into a hypobaric chamber 2 days before birth to get 28 days and 42 days CIHH mimicking 3000 m altitude (P_B=525 mmHg,P_(O_2)=108.8 mmHg), 5 h daily, respectively.The control animals were kept in the same environment as CIHH rats with free access to water and food except hypoxic exposure. The isolated hearts were perfused in the Langendorff apparatus, undergoing 30 min global ischemia and 60 min reperfusion.Cardiac function was recorded continuously during the whole experiment. Parameters of left ventricular function included left ventricular developing pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), maximal positive (+LVdp/dt) and negative (-LVdp/dt) velocity of left ventricular pressure, coronary flow (CF) and heart rate(HR).Results ① For adult rats, there was no significant difference in the parameters of left ventricular function between CIHH28 and CON28 groups. However, the recovery of cardiac function in CIHH42 rats was much better than that in CON42, including LVDP, LVEDP, ±LVdp/dt and CF (P<0.05). ② For young rats, the basic coronary flow (CF) in CIHH rats was significant higher than that in CON rats, while other parameters of cardiac function didn't change. The recovery of cardiac function in CIHH rats was much better than that in CON rats, including LVDP, LVEDP,±LVdp/dt and CF (P<0.05).Conclusion CIHH confers cardioprotection against ischemia/reperfusion injury in rat cardiomyocytes, which is predominant in CIHH42 group and significantly affected by the age of animals. Cardioprotective effects produce more easily in young rats by CIHH.
Keywords:chronic intermittent hypobaric hypoxia  adult rat  young rat  heart  ischemia/reperfusion  cardiac function
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