摘要
目的 :研究慢性低氧对大鼠肺动脉平滑肌ATP敏感钾通道 (KATP)mRNA表达的影响及新型KATP开放剂盐酸埃他卡林的作用。方法 :SD雄性大鼠 16只随机分成对照组、低氧组、低剂量治疗组 (盐酸埃他卡林 0 .75mg·kg-1·d-1,ig)、高剂量治疗组(盐酸埃他卡林 1.5mg·kg-1·d-1,ig)。将低氧组和治疗组大鼠放入常压低氧舱制备动物模型 ;采用RT PCR技术 ,分析各组肺动脉主干平滑肌KATP mR NA表达。结果 :低氧组SUR2mRNA水平显著低于正常组 ,高剂量治疗组SUR2显著高于低氧组 ,各组Kir 6 .1没有显著差异。结论 :慢性低氧抑制KATP 通道表达 ,而盐酸埃他卡林能提高表达 ,可从肺动脉高压发病机制上理解该药物治疗价值。
AIM : To study mRNA expression of ATP-sensitive potassium channels (K ATP) of pulmonary artery in chronic hypoxic pulmonary artery hypertension (CHPAH) rats and in chronic hypoxic rats treated with novel K ATP opener Iptkalim hydrochloride. METHODS : Sixteen Sprague-Dawley(SD) male rats were randomly divided into control group, hypoxic group, low dose Iptkalim group ( 0.75 mg·kg -1·d -1), and high dose Ipkalim group ( 1.5 mg·kg -1·d -1). Except the first group, the other three groups were put into hypoxic and normobaric chamber to establish chronic hypoxic model. Four weeks later, reverse transcription polymerase chain reaction (RT-PCR) was performed to analyze the mRNA level of K ATP channels in pulmonary main artery smooth muscles. RESULTS :The mRNA levels of SUR2 in the hypoxic group were significantly lower than those in the control group, this decrease was completely reversed by Iptkalim in high dose group, and no difference in Kir 6.1 mRNA level was found between four groups. CONCLUSION : K ATP channel transcriptional expression is inhibited by chronic hypoxia, and this inhibition can be up-regulated by Iptkalim. The role of potassium channel in the development of CHPAH may explain the therapeutic mechanism of Iptkalim.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2004年第4期389-393,共5页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
江苏省科委社会发展基金项目 (№BJ2 0 0 0 5 1)
江苏省教育厅基金项目 (№OOKJB3 2 0 0 0 9)
关键词
ATP敏感钾通道
低氧性肺动脉高压
盐酸埃他卡林
肺动脉平滑肌
MRNA
RT-PCR
ATP-sensitive potassium channel
chronic hypoxic pulmonary artery hypertension
Iptkalim hydrochloride
pulmonary artery smooth muscle
mRNA
RT-PCR