摘要
目的观察κ阿片受体(κopioid receptor,κ-OR)在抗大鼠心肌缺血/再灌注(ischemia and reperfusion,I/R)中的变化及其与抗I/R性心律失常的关系。方法将48只SD大鼠随机分为6组,每组8只,即对照组、U50,488H组、I/R组、U50,488H+I/R组、BNI+U50,488H+I/R组和BNI+I/R组,用于建立在体的大鼠I/R模型,观察κ-OR激动剂U50,488H对大鼠心肌I/R模型室性心律失常的影响。另取18只SD大鼠随机分为6组,每组3只,即对照组、假手术组、再灌注即刻组、60、180和360 min组,用于RT-PCR及Western blot检测I/R处理后心肌组织中κ-ORmRNA转录及其蛋白的表达。结果对照组偶发早搏,I/R组心律失常的发生率明显增加(P<0.01)。给予U50,488H可以明显降低I/R引起的室速和室颤的发生率(P<0.01)及心律失常的评分(P<0.05)。U50,488H抗心律失常的作用可被选择性的κ-OR拮抗剂nor-BNI完全阻断(P<0.01),而nor-BNI本身对I/R所致心律失常没有影响。RT-PCR的结果发现,κ-OR mRNA的转录水平在再灌注的即刻、再灌注后60及180 min时,明显高于对照组(P<0.01),在60 min时达到高峰,360 min时恢复到正常水平。Western blot检测表明,在再灌注的即刻、再灌注后60,180和360 min时,κ-OR蛋白的表达量均明显高于对照组(P<0.05)。结论在心肌I/R时,κ-OR基因的转录和其蛋白表达的水平明显上调,可能与其抗I/R性心律失常的作用相关。
AIM To investigate the anti-arrhythmic effect of x-opioid receptor （K-OR） and its changes during myocardial ischemia and reperfusion （I/R）. METHODS Forty-eight Sprague- Dawley rats were randomly divided into 6 groups with 8 rats in each group： （1）Control group, （2）Control ＋ US0,488H group, （3）I/R group, （4）US0,488H ＋ I/R group, （5）US0,488H ＋ nor-BNI ＋ I/R group, and （6）nor-BNI ＋ I/R group. This protocol was used to set up the animal model of myocardial I/R and investigate the effect on ventricular arrhythmic of K-OR agonist, U50,488H, during I/R. Other Eighteen Sprague- Dawley rats were randomly divided into 6 groups with 3 rats in each group： （1）Control group, （2）Sham operation group, （3）I/R 0 min group, （4）I/R 60 rain group, （5）I/R 180 min group, and （6）I/R 360 rain group. This protocol was used to investigate the levels of k-OR mRNA and its protein in rats heart at different time points during I/R by RT-PCR and Western blot, respectively. RESULTS Few ventricular premature contractions were observed in control group and the incidence of arrhythmia in I/R group significantly increased （P 〈0. 01 ）. With pretreatment of U50,488H, the incidence of ventricular tachy- cardia and ventricular fibrillation （ P 〈 0.01 ） was reduced as well as arrhythmia score in I/R group （P 〈 0. 05）. With pretreatment of selective K-OR antagonist （nor-BNI）, the anti-arrhythmic effect of U50,488H was completely blocked （P 〈0.01）. But it had no effect on the arrhythmia induced by I/R （P 〉 0. 05 ）. Compared with those in control group, the levels of K-OR mRNA was significantly increased at 0 min, 60 min and 180 min during reperfusion （P 〈0.01 ） and increased to utmost amount at 60 min, but decreased to the normal level at 360 min; compared with those in control group, the density of K-OR protein increased significantly at 0 min, 60 min, 180 min and 360 rain during reperfusion （P 〈 0. 05 ）. CONCLUSION During myocardial I/R, the transcription of K-OR mRNA and the expression of its protein are increased, which may be related to the anti-arrhythmia effect during myocardial I/R.
出处
《心脏杂志》
CAS
2009年第3期317-320,328,共5页
Chinese Heart Journal
基金
国家自然科学基金面上项目资助(30770802及30370580)
全军医药卫生科研基金军队"十一五"计划面上项目资助(06MA203)
