新型K_(ATP)开放剂埃他卡林对慢性低氧诱导大鼠体内肺动脉平滑肌K_(ATP)通道mRNA表达变化的影响

目的研究慢性低氧对大鼠肺动脉平滑肌KATP通道mRNA表达的影响及新型KATP开放剂埃他卡林(Iptakalim,IPT)的作用。方法将清洁级SD大鼠30只随机分成对照组、低氧组、IPT组,每组10只。将低氧组与IPT组放入常压低氧舱制备动物模型;采用右心导管测量大鼠肺动脉压;用实时荧光定量PCR检测(Real time PCR)技术分析各组肺动脉平滑肌KATP通道Kir6.1与SUR2B mRNA表达。结果低氧组大鼠肺动脉平均压高于对照组和IPT组(P<0.05),低氧组SUR2B亚基mRNA水平低于对照组(P<0.05),IPT可逆转慢性低氧对SUR2B的作用,各组Kir6.1亚基mRNA表达水平无差异(P>0.05)。结论慢性缺氧导致大鼠肺动脉平滑肌KATP通道SUR2B mRNA表达减少,IPT能拮抗慢性缺氧对KATP通道SUR2B mRNA基因表达的抑制作用。

Effects of iptakalim, a novel KATP opener,on chronic hypoxia-induced the changes of mRNA expression of KATP channel in pulmonary arterial smooth muscle of rats in vivo

Aim To investigate the effect of chronic hypoxia on the expression of KATP channel subtype’s mRNA in pulmonary arterial smooth muscle of rats and the effects of new KATP opener iptakalim.Methods Thirty male SD rats were randomly divided into three groups: the control group and the two hypoxic groups consisting of simple hypoxic groups,treatment group with 10 rats each.Rats in hypoxic group and IPT group were placed into a normobaric hypoxia (10%±0.5% oxygen)chamber.Right heart catheterization was used to measure pulmonary arterial pressure in rats.Real time PCR was used to detect the expression of Kir6.1 and SUR2B mRNA in pulmonary arterial smooth muscle of rats in the three groups.Results Mean pulmonary arterial pressure(MPAP) was significantly higher in hypoxic group than those in control group and IPT group(P<0.05). The mRNA expression of SUR2B was significantly lower in hypoxic group than those in control group(P<0.05) and IPT antagonized the effect of chronic hypoxia. There was no significant difference in the mRNA expression of Kir6.1 among three groups(P>0.05).Conclusion The mRNA expression of SUR2B of KATP channel is inhibited by chronic hypoxia,and this inhibition can be reversed by novel KATP opener Iptkalim.