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机构地区:[1]第四军医大学药学系药理学教研室 [2]空军北京95830部队门诊部
出 处:《心脏杂志》2010年第5期647-649,663,共4页Chinese Heart Journal
基 金:国家自然科学基金项目资助(30570757)
摘 要:目的:探讨P2Y受体激动剂尿苷三磷酸(UTP)对于大鼠心脏缺血/再灌注损伤(I/RI)的延迟性拈抗作用。方法:24只SD大鼠随机分为4组:实验对照组、UTP组、UTP+苏拉明(suramin,SRM)组及SRM组。所有大鼠尾静脉给药24h后,建立Langendorff离体心脏灌流模型。平衡10min后全心停灌,25min后复灌,持续再灌40min。观察心脏再灌注前后血流动力学指标及心肌超微结构,记录心脏表面心电图计算心律失常的发生率,收集冠脉流出液,用全自动生化分析仪测量乳酸脱氢酶(LDH)的水平:结果:复灌后第5min和25min时,UTP组的左室发展压(LVDP)、左室压力微分(±ap/dtmax)恢复率均优于实验对照组(P〈0.05,P〈0.01);冠脉流出液中LDH的水平明显值降低(P〈0.01);复灌第5—15min和第25~35min时的心律失常的发生频率均显著下降(P〈0.05,P〈0.01);心肌超微结构的损伤减轻。而以SRM与UTP同时作用后,UTP对心脏的保护作用则被取消。SRM组与实验对照组相比各项指标无明显变化。结论:UTP预处理可对心脏I/RI产生延迟性拈抗作用;而P2Y受体拮抗剂SRM可取消这种作用,表明UTP对心脏的保护作用是通过P2Y受体介导的。AIM: To study the cardioprotective effect uridine triphosphate (UTP) on ischemia/reperfusion injuries of rat hearts and to explore whether this effect of UTP is mediated by P2Y receptor. METHODS: Twenty-four Sprague Dawley (SD) rats were divided into four groups: control group (0. 9% sodium chloride i. v. ), UTP group (4. 4 μg/kg i. v. ), UTP and suramin (antagonist of P2Y receptor) group (4.4 μg/kg i.v. + 30 μg/kg i. v. ) and suramin group (30 p.g/kg i. v. ). Twenty-four h after drug injection, rat hearts were isolated and perfused with K-H solution by Langendorff system. The hearts were subjected to 25 rain ischemia followed by 40 min reperfusion. Hemodynamic indexes were measured and ECG was recorded. The coronary effluent was collected to measure the lactate dehydrogenase (LDH) level. Ultra- structure of myocardium was observed by transmission electron microscope. RESULTS: Twenty-five rain after ischemia, significantly better recovery percentage of left ventricular function (P 〈 0.05, P 〈 0.01 ) and lower LDH level and arrhythmia incidence rate ( both P 〈 0.01 ) were observed in UTP group compared with those in control group. The myocardial ultrastructure of the UTP group was generally normal and the cardioprotective effects of UTP were eliminated by suramin. CONCLUSION: UTP pretreatment protects rat hearts from ischemia/reperfusion injury., which is cancelled by P2Y receptors' antagonist suramin, indicating that the myocardial protective effect of UTP is mediated by P2Y receptors.
关 键 词:缺血/再灌注损伤 心脏 P2受体 尿苷三磷酸 大鼠
分 类 号:G804[文化科学—运动人体科学] R542.2[文化科学—体育学]
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