环孢素A对大鼠缺血再灌注心肌嘌呤代谢的影响

Effect of ciclosporin A on purine metabolism in rats with myocardial ischemia-reperfusion injury

目的:研究环孢素A(CsA)对大鼠心肌缺血再灌注时嘌呤代谢的影响及其可能的心肌保护机制。方法:48只大鼠随机分为3组:对照组、缺血再灌注组和药物处理组,每组16只。应用Langendorff离体心脏灌注模型对大鼠离体心脏进行逆行灌注。对照组应用K-B液持续灌注90 min。缺血再灌注组(再灌组):离体心脏逆行灌注平衡10 min,再持续灌注20 min后转变为30 min心脏缺血,之后30 min再灌注。药物处理组(CsA组):离体心脏逆行灌注平衡10 min,用含有0.2μmol/L CsA的K-B液灌注20 min后转变为30 min心脏缺血,之后30 min再灌注。每组取8只心脏进行TTC染色测心肌梗死面积;其余8只于总过程90 min后接取冠状动脉流出液2 mL用于嘌呤碱各组分的测定及LDH活性的测定,并将心肌研磨后离心,上清用于测定嘌呤核苷酸磷酸化酶(PNPase)的活性。结果:与缺血再灌注组相比,CsA组心肌梗死面积及冠脉流出液中LDH活性明显降低,嘌呤释放明显减少,次黄苷和腺苷明显增多,尿酸明显减少。CsA组心肌匀浆液中PNPase活性较再灌注组明显降低。结论:CsA在心肌缺血再灌注过程中对心肌具有保护作用,其机制可能是影响了心肌嘌呤的代谢过程。

Objective： To study the effect of ciclosporin A（CsA） on purine metabolism in rats with myocardial ischemia-reperfusion injury and its possible mechanism of myocardial protective effect.Methods： Myocardial ischemia-reperfusion models of 48 rat hearts was established with Langendorff model.48 hearts were randomly divided into control group,reperfused group and CsA group.Control group were perfused with K-B solution for 90 min.Reperfused group were subjected to ischemia and reperfusion after 30 min perfusion with KB solution.CsA group were also subjected to ischemia and reperfusion after 30 min perfusion,but CsA 0.2 μmol/L were added into the perfusate during the later 20 min perfusion.The purine releases in the coronary artery effluent after the whole process and the activities of PNPase in the myocardial tissue were measured by HPLC.The activities of the effluent of coronary artery lactate dehydrogenase（LDH） and myocardial infarction size in myocardial tissue were assayed.Results： Ciclosporin A depressed the activity of coronary artery LDH and myocardial infarction size,and significantly increased the release of adenosine and inosine,decreased the release of uric acid after ischemia/reperfusion.CsA also depressed the activities of PNPase and decreased total release of purine in injured myocardial tissue.Conclusion： Ciclosporin A protects the myocardial tissues from the ischemia-reperfusion injury with a possible mechanism of intervening the metabolism of purine.