丹曲林对大鼠缺血再灌注心肌能量代谢的影响  

Effect of dantrolene on energy metabolism in rats with myocardial ischemia-reperfusion

作　　者：赵晓丽[1] 李海东[1] 郭彦青[1] 王丽艳[1] 曹颖[1] 于公元[1] 张艳君[1] 

机构地区：[1]天津医科大学生物化学教研室,300070

出　　处：《中华医学杂志》2011年第2期117-120,共4页National Medical Journal of China

基　　金：基金项目：天津市教育委员会科研项目（200011）;天津医科大学科学基金（2009KX07）;天津市科学技术委员会科研项目（08JCYBJC27400）

摘　　要：目的探讨丹曲林对大鼠心肌缺血再灌注过程中能量代谢的影响。方法48只健康雄性Wistar大鼠分为对照组、缺血再灌注组和丹曲林处理组，建立Langendorff离体心脏灌注模型。各组均先用Krebs液灌注平衡30rain。缺血再灌注组在平衡30min后全心缺血30min，再灌注60min；丹曲林处理组Krebs液中加入5μmol／L丹曲林。以氯化四唑染色法观察心肌梗死面积，并用乳酸脱氢酶（LDH）活性和血液动力学变化评估心肌损伤程度。采用高效液相色谱法测定心肌组织中高能磷酸化合物，以及嘌呤核苷酸补救合成的两个酶，次黄嘌呤（鸟嘌呤）磷酸核糖转移酶（HGPRT）和腺嘌呤磷酸核糖转移酶（APRT）的活性，来研究丹曲林对缺血再灌注心肌能量代谢的影响。结果丹曲林处理的心肌梗死面积和LDH释放均显著低于缺血再灌注组[22．1％比25．3％、（70±6）U／g比（116±10）U／g，均P〈0．05]；丹曲林对缺血再灌注心脏的血液动力学没有明显作用，只是冠脉流量有轻微增加。丹曲林处理组高能磷酸化合物含量明显高于缺血再灌注组（P〈0．05），而HGPRT和APRT的活性均显著低于缺血再灌注组[（7．63±0．72）nmol·mg^-1·min^-1比（12．42±1．12）nmol·mg^-1·min^-1、（4．14±0．22）nmol·mg^-1·min^-1比（4．57±0．39）nmol·mg^-1·min^-1，均P〈0．05]。结论丹曲林减轻缺血再灌注损伤，显著促进再灌注心肌的能量代谢，对心肌有保护作用。Objective To investigate the effect of dantrolene on energy metabolism in rats with myocardial ischemia-reperfusion. Methods Forty-eight male rats were randomly divided into 3 groups： control group, ischemia-reperfusion group and dantrolene treatment group. With a Langendorff model system, the hearts were perfused with Krebs buffer for 30 min as pre-ischemia control. For ischemia- reperfusion, the hearts were subjected to global ischemia for 30 rain and reperfusion for 60 min. The dantrolene treatment group was perfused in the presence of 5 μmol/L dantrolene before ischemia. Tetrazolium chloride （Trc） staining, lactate dehydrogenase （LDH）. release and hemodynamics were used to evaluate the tissue injuries. The effect of dantrolene on energy metabolism was evaluated by measuring the quantity of high-energy phosphates and the activity of 2 enzymes in purine salvage synthesis： hypoxanthine- guanine phosphoribosyl transferase （HGPRT） and adenine phosphoribosyl transferase （APRT） by high- performance liquid chromatography （HPLC）. Results The myocardial infarct size and LDH release in dantrolene treatment group were lower than those of ischemia-reperfusion hearts [ 22.1% vs 25.3%, （70± 6） U/g vs （116 ±10） U/g, both P〈0.05]. Dantrolene had no effect on the hemodynamics, except for a slight increase in coronary flow. The hearts receiving dantrolene showed a significantly higher levels of high- energy phosphates and a lower activity of HGPRT and APRT than those in the ischemia-reperfusion group [（7.63±0.72）nmol·mg^-1·min^-1 vs（12.42±1.12）nmol·mg^-1·min^-1、（4.14±0.22）nmol·mg^-1·min^-1vs（4.57±0.39）nmol·mg^-1·min^-1, both P 〈 0. 05 ]. Conclusion Dantrolene is nun vs （4. 57 ± 0. 39 ） nmol · mg-1 . -1 cardioprotective for ischemia-reperfusion injury through reducing infarct size and improving energy metabolism.

关 键 词：心肌缺血 再灌注损伤 能量代谢 丹曲林 

分 类 号：R965[医药卫生—药理学]