新型钾通道开放剂对心血管ATP-敏感性钾通道基因表达的调节作用

REGULATION BY POTASSIUM CHANNEL OPENERS ON GENE EXPRESSION OF ATP-SENSITIVE POTASSIUM CHANNELS IN RAT CARDIOVASCULAR SYSTEM

目的:研究脂肪胺类的新型钾通道开放剂(KCO)埃他卡林(Ipt)和氰胍类的KCO吡那地尔(Pin)对大鼠心血管ATP-敏感性钾通道(KATP)的亚基SUR1、SUR2、Kir6.1和Kir6.2等在mRNA水平的调节作用。方法:SD大鼠给药1周后处死并取组织,提取总RNA,利用反转录-聚合酶链式反应(RT-PCR)研究以上基因在mRNA水平的改变。结果:与正常对照相比,心脏组织中,Ipt和Pin对KATP的4个亚基在mRNA水平均无显著影响;主动脉平滑肌上,Ipt对4个亚基的mRNA表达无显著影响,但Pin可显著上调SUR2的mRNA表达;尾动脉平滑肌上,Ipt对Kir6.1/Kir6.2、Pin对SUR2/Kir6.1均有显著下调的作用。结论:心肌、大动脉平滑肌和小动脉平滑肌KATP基因表达的调控不同,Ipt选择性调节小动脉平滑肌Kir6.1/Kir6.2;Ipt对心血管KATP基因表达的调节作用不同于Pin。

The present study described the effects of iptakalim and pinacidil, which belong to two different chemical structures of potassium channel opener （KOD）, on mRNA expression for subunits of ATP-sensitive potassium channel （KATP）, including SUR1, SUR2, Kir6.1, and Kir6.2. Methods： Reverse transcription-polymerase chain reaction （RT-PCR） using primers specific for these four subunit genes was performed on total RNA from rat tissues of heart, aortic smooth muscle and tail artery smooth muscle, after iptakalim and pinacidil administration for one week. Results： Compared with the normal control group without drug administration, in heart tissue, iptakalim and pinacidil showed no significant effects on mRNA levels of the four subunits of KATP. In endothelium-free aortic smooth muscle, SUR2 mRNA level was up-regulated significantly in pinacidil group, while no subunits were changed by iptakalim treatment. In endothelium - free tail artery smooth muscle, Kir6.1 and Kir6.2 mRNA levels were reduced significantly in iptakalim group, and SUR2 and Kir6.1 in pinacidil group. Conclusion： The gene expression patterns of KATP were different among tissues of heart, large artery and small artery. Iptakalim selectively down-regulated the mRNA levels of Kir6.1 and Kit6.2 in smooth muscle of small arteries, and the regulation effect of iptakalim on KATP was different from that of pinacidil in cardiovascular system.