腺苷A_1受体激动剂R-苯异丙基腺苷介导的大鼠心肌延迟预适应

Adenosine A_1 receptor agonist R-PIA induces delayed myocardial preconditioning in rats

目的 研究腺苷A1受体激动剂R 苯异丙基腺苷 (R PIA)能否介导大鼠心脏产生延迟预适应。方法 取雄性Wistar大鼠 48只 ,随机分为 3组。A组 :生理盐水 0 .2ml/只 ;B组 :R PIA 0 .0 3mg/kg ;C组 :R PIA 0 .0 3mg/kg +DPCPX 0 .2mg/kg。大鼠经皮下注射给药后 2 4h开胸 ,结扎左冠状动脉前降支 30min、再灌注 12 0min ,摘取心脏 ,用于梗死范围测定 (TTC染色法 )、原位心肌细胞凋亡 (TUNEL法 )检测。结果 大鼠体重及左室重量组间差别无显著性 (P >0 .0 5 )。R PIA组心肌梗死范围显著低于生理盐水组及R PIA +DPCPX组 (P均 <0 .0 1) ,而生理盐水组与R PIA +DPCPX组比较差异无显著性意义 (P >0 .0 5 )。生理盐水组、R PIA组及R PIA +DPCPX组心肌凋亡细胞计数 (个 /高倍视野 )组间差异无显著性意义 (P >0 .0 5 )。结论 R PIA可使大鼠在体心脏产生延迟预适应 (显著降低心肌梗死范围 ) ;R PIA对 2 4h后缺血再灌注损伤所致的心肌细胞凋亡可能无影响。

Objective To investigate if R Phenylisopropyladenosine (R PIA) may induce delayed preconditioning in situ heart of rat.Methods Forty eight male Wistar rats were randomly divided into three groups(n=16 in each group).Group A,normal saline 0.2 ml/rat sc;Group B,R PIA 0.03 mg·kg -1 sc;Group C,R PIA 0.03 mg·kg -1 sc and 1,3 dipropyl 8 cyclopentylxanthine(DPCPX) 0.2 mg·kg -1 sc.Twenty four hours after above drugs were injected,the chest of rat was opened and the rats were subjected to regional myocardial ischemia for 30 min followed by reperfusion for 120 min,and then the hearts of the rats were taken for infarct size determination (TTC stain) and fixed in 4% paraformaldehyde solution for determination of cardiac myocyte apoptosis in situ tissue section (TUNEL assay).Data were presented as ±s and analyzed by one way analysis of variance(ANOVA) with repeated measurements,followed by q test.Results There was no significant difference in body weight and left ventricular weight of the rats between groups (P>0.05).The infarct size in Group B,expressed as percentage of left ventricular weight,was significantly smaller than those in Group A (P<0.01) and Group C (P<0.01),yet there was no significant difference between Group A and Group C (P>0.05). ANOVA showed no significant difference in cardiac myocyte apoptosis counts between groups (P>0.05).Conclusions The R PIA,a stable specific adenosine A 1receptor agonist,may mediate delayed myocardial preconditioning which reduces significantly the infarct size of myocardium in rats.The R PIA has no effect on myocyte apoptosis induced by ischemia reperfusion 24 hours after its subcutaneous administration in rats.