丹曲林对大鼠缺血-再灌注心肌嘌呤代谢的影响  

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

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

机构地区：[1]天津医科大学生物化学教研室,300070

出　　处：《中国急救医学》2011年第6期526-530,共5页Chinese Journal of Critical Care Medicine

基　　金：天津市教育委员会科研项目（No.200011）;天津医科大学科研基金项目（No.2007KY01;No.2007KY03）

摘　　要：目的探讨丹曲林对大鼠缺血-再灌注心肌嘌呤代谢的影响。方法24只健康雄性Wistar大鼠分为三组：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，对照组心脏用Krebs液灌注平衡30min；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，缺血30min，再灌注60min。TTC染色观察心肌梗死面积，检测乳酸脱氢酶（lactate dehydrogenase，LDH）活性，采用高效液相色谱法（HPLC）测定灌流液嘌呤代谢产物：腺苷、次黄苷、次黄嘌呤、黄嘌呤和尿酸，检测嘌呤代谢途径的酶5’-核苷酸酶（5’nucleotidase，5＇-NT）、腺苷脱氨酶（adenosine deaminase，ADA）、嘌呤核苷磷酸化酶（pufine nucleoside phosphorylase，PNP）及黄嘌呤氧化酶（xanthine oxidase，XO）的活性。结果丹曲林预处理后，缺血-再灌注心肌梗死面积减少12．6％，LDH活性降低39．7％；腺苷、次黄苷、次黄嘌呤、黄嘌呤和尿酸较缺血-再灌注组分别下降30．9％、22．1％、19．5％、25．4％和12．7％（P〈0．05）；5’-核苷酸酶、腺苷脱氨酶和黄嘌呤氧化酶的活性较缺血-再灌注心肌显著增加（P〈0．01），嘌呤核苷磷酸化酶的活性显著降低（P〈0．05）。结论丹曲林保存细胞内的代谢酶活性，显著提高缺血-再灌注心肌的能量恢复，对心肌缺血-再灌注损伤具有保护作用。Objective To investigate the effect of dantrolene on purine metabolism in rats with myocardial ischemia - reperfusion. Methods Twenty - four male rats were randomly divided into three groups： control group, ischemia - reperfusion group and dantrolene - treated group. The hearts were peffused in a Langendor/f model system. Hearts were per/used with Krebs for 30 rain as a preischemic control. For ischemia - reperfusion measurement, hearts were subjected to further 30 min period of myocardial ischemia and 60 min of reperfusion. The dantrolene - treated group was subjected to perfusion in the presence of the 5 μmoL/L dantrolene before ischemia and reperfusion. Tetrazoliurn chloride （TFC） staining, lactate dehydrogenase （LDH） release were used to evaluate the tissue injury. The levels of adenosine, inosine, bypoxanthine, xanthine, uric acid, and the activity of four enzymes in purine metabolism： 5＇ - nucleotidase （5＇ - NT ）, adenosine deaminase （ADA）, purine nueleoside phosphorylase （PNP）, and xanthine oxidase （XO） were measured by high -performance liquid chromatography （HPLC）. Results Pretreaed with 5 I^mol/L dantrolene, the myocardial infarction size was decreased by 12.6% , LDH release was decreased by 39.7%. The levels of purine metabolites in dantrolene - treated group were significantly decreased as compared with isehemia - reperfusion group （ P 〈 0.05 ）. The content of adenosine, inosine, hypoxanthine, xanthine and uric acid was decreased to 69. 1% , 77.9% , 80. 5% , 74.6% and 87.3% of ischemia - reper/usion myocardium, respectively.The activity of 5＇ -NT, ADA, and XO in dantrolene -treated group was significantly increased （P 〈 0. 01 ） , and the activity of PNP was significantly reduced as compared with ischemia - reperfusion group （P 〈 0.05 ）. Conclusion Pretreatment with dantrolene preserves the intracellular enzyme activity, significantly improves energy metabolism and produces a cardioprotective effect against ischemia- reperfusion injury.

关 键 词：心肌缺血 再灌注损伤 嘌呤代谢 丹曲林 

分 类 号：R654.2[医药卫生—外科学]