慢性缺氧对大鼠肺动脉和右心室内皮素与一氧化氮合成酶mRNA表达的影响

Expression of endothelin-1 mRNA, endothelin recep-tor-A and nitric oxide synthase mRNA in pulmonaryartery and right ventriculus cordis of rat exposed tohypoxia

为了解慢性缺氧时肺动脉和右心室内皮素与一氧化氮合成酶（ＮＯＳ）ｍＲＮＡ表达的变化，作者应用逆转录多聚酶链反应（ＲＴ－ＰＣＲ）技术检测了缺氧大鼠肺动脉和右心室内皮素１（ＥＴ－１）、内皮素受体Ａ（ＥＴＲ－Ａ）及ＮＯＳｍＲＮＡ的表达水平。结果显示（１）缺氧１周后肺动脉ＥＴ－１由正常对照的７９２８７±９０２６（单位为闪烁计数／ｍｉｎ，下同）增加到１０３５２６±１１９２３（Ｐ＜０．０５）；２周后降至８０６４０±７８４３（Ｐ＞０．０５）；３周后上升到１００１９８±１３７１２（Ｐ＜０．０５）。肺动脉ＥＴＲ－Ａ于缺氧１周和２周时变化不明显，３周后由对照的３２５６３±７２６４上升到５０６２７±８２２３（Ｐ＜０．００１）。ＮＯＳ于缺氧１、２、３周时分别为２８１３７±４５１７，２８４３３±４６６７，２９８４０±４４２８，均低于正常对照（３９９１７±７６９２）。（２）缺氧２周后，右心室ＥＴ－１ｍＲＮＡ变化不明显，而ＥＴＲ－Ａ较对照（２８５３３±３３７９）明显增加（４０２４５±６５４０）（Ｐ＜０．０５）；缺氧３周后ＥＴ－１及ＥＴＲ－Ａ均明显升高。ＮＯＳ在缺氧２周和３周后均无明显变化。提示缺氧可刺激／或抑制肺动脉及右心室内ＥＴ－１及Ｎ?

ndothelins(ETs)are a family of novel regulato-ry peptides which can constrict the vascular and pro-mote the proliferation of vascular smooth muscle cells.Serum ET-1 was elevated, and nitric oxide (NO) lev-els were reduced in hypoxic pulmonary hypertension.However, the exact mechanism remains unclear, andno study has elucidated if hypoxia could stimulate di-rectly overgrowth of right ventricle in patients withchronic cor pulmonale. To investigate the role of ET-1and NO in hypoxiainduced pulmonary hypertensionand right ventricular hypertrophy, we measured thelevels of ET-1 mRNA, ET receptorA (ETR-A) mR-NA and nitric oxide svnthase (NOS) mRNA in thepulmonary artery and right ventricle of rats exposed tohypoxia (FiO = 0.1, 8 hours daily for 1 , 2 and 3weeksl by reverse transcription-polymerase chain reac-tion (RT-PCR). ET-1 mRNA level of pulmonaryartery raised after 1 week's hypoxia (P<0. 05) , andafter 2 weeks' hypoxia , it returned to near normal, butelevated significantly again after 3 weeks' hypoxia.Pulmonary artery ETR-A mRNA in 1 and 2 weeks hy-poxic groups showed no significant change, but itraised significantly in 3 weeks' hypoxic group. Afterexposure to hypoxia for 1 , 2 and 3 weeks, NOS mR-NA in the pulmonary artery all reduced significantly (p<0. 05). The right ventriculus cordis showed a signifi-cant increase in weight after 3 and 2 weeks, hypoxia,ET-1 mRNA showed no significant change but ETR-AmRNA increased significantly after 2 weeks' hypoxia:both ET-1 mRNA and ETR-A mRNA showed signifi-cant increase in rat right ventricle after 3 weeks, hy-poxia. In the ventriculus cordis of rats exposed to hy-poxia for 2 and 3 weeks, NOS nRNA had no signifi-cant change.