埃他卡林对人肺动脉内皮细胞内皮素系统的作用

Effects of iptakalim on the functions of endothelin system in human pulmonary artery endothelial cells

目的研究新型ATP敏感性钾通道(KATP)开放剂埃他卡林(iptakalim,IPT)对人肺动脉内皮细胞内皮素(ET)系统的作用。方法原代培养人肺动脉内皮细胞(HPAECs),分别加入不同浓度埃他卡林,共同孵育24h后;应用放射免疫法测定各组细胞上清内皮素-1(ET-1)浓度的变化,同时用逆转录多聚酶链反应(RT-PCR)方法检测各组细胞ET-1及内皮素转换酶(ECE)mRNA表达的变化。结果在IPT浓度为10-6mol·L-1及以上时,能够剂量依赖性地抑制HPAECs合成分泌ET-1,同时也降低ET-1mRNA的表达量;在IPT浓度为10-7mol·L-1及以上时,能够剂量依赖性地降低ECEmRNA的表达量。结论IPT通过抑制人肺动脉内皮细胞ET-1和ECEmRNA的表达量,继而抑制内皮细胞合成分泌ET-1,可能成为较有前途的治疗肺动脉高压的有效药物。

Aim To investigate the effects of iptakalim （IPT） ,a novel K ATP opener,on the functions of endothelin system in human pulmonary artery endothelial cells. Methods Primary cultured human pulmonary artery endothelial cells were incubated with different concentrations iptakalim for 24 h. The levels of ET-1 in medium were observed by radioimmunoassay. Reverse transcription polymerase chain reaction （RT-PCR）was performed to analyze the expression of ET-1 and ECE. Results When endothelial cells were incubated with IPT at concentrations above 10 μmol · L^-1, the levels of ET-1 release in medium and the levels of ET-1 mRNA were significantly inhibited. When endothelial cells were incubated with IPT at concentrations above 1 μmol · L^-1,the levels of ECE mRNA were significantly inhibited. Conclusions IPT can inhibit the expression of ET-1 and ECE mRNA from human pulmonary artery endothelial cells, thus it inhibits the secretion of ET-1 from endothelial cells. Iptakalim may serve as a promising candidate drug to treat pulmonary hypertension.