Jin-Cheng Liu, Wen Yin, Zhao Yin, Quan-Yu Zhang, Shu-Miao Zhang, Hai-Tao Guo, Hui Bi, Yue-Min Wang, Xin Sun, Liang Cheng, Qin Cui, Shi-Qiang Yu, Kaye Alan D, Ding-Hua Yi, Jian-Ming Pei
Department of Physiology, National Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Arch Med Res. 2008 Jul;39(5):483-8. doi: 10.1016/j.arcmed.2008.02.011.
It remains unclear whether the kappa-opioid receptor (kappa-OR) is altered during ischemia and reperfusion. Therefore, the present study was designed to investigate changes in the kappa-OR. Additionally, the anti-arrhythmic effect induced by kappa-OR stimulation was also determined during ischemia and reperfusion (I/R).
Rats were randomly divided into different groups according to two experimental protocols. The anti-arrhythmic effects of U50,488H, a selective kappa-OR agonist, in an I/R model of 15-min ischemia were studied followed by 15 min of reperfusion. The content of kappa-OR mRNA and protein were measured by RT-PCR and Western blotting techniques in an I/R model of 30-min ischemia followed by 360 min of reperfusion.
Limited numbers of premature ventricular contractions (PVCs) were revealed in the control group. Administration of U50,488H in the control group had no effect on occurrence of PVCs. Incidence of arrhythmia in the I/R group was significantly increased. Treated with U50,488H in the I/R group, the incidence of arrhythmia was significantly reduced. With prior use of nor-BNI, a selective kappa-OR antagonist, the anti-arrhythmic effect of U50,488H was completely blocked. Compared with the control group, the content of kappa-OR mRNA and the density of kappa-OR protein increased significantly at 0 min, 60 min, and 180 min during reperfusion.
The present study provides evidence for the first time that the expressions of kappa-OR mRNA and protein are upregulated in the heart of I/R rats. This alteration may produce a strengthened anti-arrhythmic effect upon kappa-OR stimulation during I/R.
κ-阿片受体（kappa-OR）在缺血再灌注过程中是否发生改变尚不清楚。因此，本研究旨在调查kappa-OR的变化。此外，还确定了在缺血再灌注（I/R）期间kappa-OR刺激诱导的抗心律失常作用。
根据两种实验方案将大鼠随机分为不同组。研究了选择性kappa-OR激动剂U50,488H在15分钟缺血再灌注15分钟的I/R模型中的抗心律失常作用。通过RT-PCR和蛋白质印迹技术在30分钟缺血再灌注360分钟的I/R模型中测量kappa-OR mRNA和蛋白质的含量。
对照组出现少量室性早搏（PVCs）。对照组给予U50,488H对PVCs的发生无影响。I/R组心律失常的发生率显著增加。I/R组用U50,488H治疗后，心律失常的发生率显著降低。预先使用选择性kappa-OR拮抗剂nor-BNI后，U50,488H的抗心律失常作用被完全阻断。与对照组相比，再灌注期间0分钟、60分钟和180分钟时kappa-OR mRNA的含量和kappa-OR蛋白的密度显著增加。
本研究首次提供证据表明，I/R大鼠心脏中kappa-OR mRNA和蛋白的表达上调。这种改变可能在I/R期间对kappa-OR刺激产生增强的抗心律失常作用。
