CAJ | 학술논문

目的研究新型ATP敏感性钾通道(K_(ATP))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24 h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~(-6) mol·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-1 mRNA的表达量;在IPT浓度为10~(-7) mol·L~(-1)及以上时,能够剂量依赖性地降低ECE mRNA的表达量.结论 IPT通过抑制人肺动脉内皮细胞ET-1和 ECE mRNA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.
목적 연구신형ATP민감성갑통도(K_(ATP))개방제애타잡림(iptakalim,IPT)대인폐동맥내피세포내피소(ET)계통적작용.방법 원대배양인폐동맥내피세포(HPAECs),분별가입불동농도애타잡림,공동부육24 h후;응용방사면역법측정각조세포상청내피소-1(ET-1)농도적변화,동시용역전록다취매련반응(RT-PCR)방법 검측각조세포ET-1급내피소전환매(ECE)mRNA표체적변화. 결과 재IPT농도위10~(-6) mol·L~(-1)급이상시,능구제량의뢰성지억제HPAECs합성분비ET-1,동시야강저ET-1 mRNA적표체량;재IPT농도위10~(-7) mol·L~(-1)급이상시,능구제량의뢰성지강저ECE mRNA적표체량.결론 IPT통과억제인폐동맥내피세포ET-1화 ECE mRNA적표체량,계이억제내피세포합성분비ET-1,가능성위교유전도적치료폐동맥고압적유효약물.
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.