腺苷A_1受体激动剂诱导心脏缺血预处理延迟效应的实验研究

Experimental study of heart delayed preconditioning induced b y adenosine A_1 receptor agonist in rat heart

目的 探讨腺苷 A1 受体激动剂能否诱导心脏缺血预处理的延迟保护及其与锰 -超氧化物歧化酶 (Mn-SOD)表达的关系。 方法 按随机数字表法将 6 0只鼠分为 6组 ,每组 10只。 A组 :用腺苷 A1 受体激动剂 2 -氯环戊腺苷 (CCPA)预处理 ;B组 :为缺血对照 ,静脉注射生理盐水 ;C组 :注射反义全巯代磷酸化寡核苷酸 (ODN)后再注射生理盐水 ;D组、E组和 F组在预处理前分别静脉注射 Mn- SOD反义 ODN、意义 ODN、错配 ODN。观察左心室压力变化最大速率 (±dp/ dtmax)的恢复率 ,肌酸激酶同工酶 (CK- MB)释放活性 ,心肌三磷酸腺苷 (ATP)、丙二醛 (MDA)含量和 Mn- SOD活性。 结果 A组、E组和 F组± dp/ dtmax恢复率、心肌 ATP含量和 Mn- SOD活性均高于 B组、C组和D组 (P<0 .0 5 ,0 .0 1) ,而 CK- MB释放活性和 MDA含量均低于 B组、C组和 D组 (P<0 .0 5 )。 结论 腺苷 A1 受体激动剂可诱导预处理的延迟效应 ,减轻心肌缺血 -再灌注损伤 ,其机制与 Mn- SOD的高表达有关。

Objective To investigate whether adenosine A 1 re cept or agonist can trigger delayed phase of ischemic preconditioning and reduce isch emia-reperfusion injury in rat heart, in which manganese superoxide dismutase (Mn-SOD) expression is involved. Methods Sixty adult health m ale Wistar rats were divided into 6 groups according to the random digital tabl e (each group 10 rats). Group A: pretreated with 2-chloro-N6-cyclopen-tylade nosine (CCPA), group B: injected with normal saline only, the vehicle of CCPA as control, group C: merely injected with antisense phosphorothioated oligodeoxynucleotide (ODN) to t he initiation site of rat Mn-SOD mRNA and then with normal saline. The antisen se, sense and scrambled phosphorothioated ODN to the initiation site of rat Mn -SOD mRNA were given in group D, group E and group F before preconditioning w ith CCPA. The left ventricular developing pressure (±dp/dt max) recovery r ate, activity of myocardial isoenzyme of creatine kinase(CK-MB) r e lease, myocardial adenosine triphosphate (ATP) and malondialdehyde (MDA) conten t, myocardial Mn-SOD activity were observed. Results The ±dp /dt max recovery rate, myocardial ATP content and activity of myocardial Mn-SOD in group A, group E, group F were much higher than those in group B, group C, group D (P<0.05,0.01), while CK-MB release activity and MDA cont ent were lower than those in group B, group C and group D (P<0.05). Conclusion This study shows that adenosine A 1 receptor agonist coul d induce delayed preconditioning and then reduce ischemia-reperfusion injury in adult health male Wistar rats, which may involve myocardial upregulating expression of Mn-SOD.