反义寡核苷酸对正常和常压缺氧大鼠肺血流动力学的作用

筛选出针对内皮素 １ （ＥＴ １） 前体基因反义硫代寡核苷酸片断（ＥＴＡＳＯＤＮ）， 已证明ＥＴＡＳＯＤＮ能显著抑制培养细胞ＥＴ １的生成（Ｐ＜ ０．０５）。通过实验观察侧脑室注射该片断对常氧和常压缺氧大鼠的作用， 发现缺氧性肺动脉高压大鼠下丘脑ＥＴ １含量显著高于常氧大鼠（Ｐ＜ ０．０５）； 侧脑室内注ＥＴＡＳＯＤＮ 能显著降低常氧和缺氧大鼠下丘脑ＥＴ １水平（Ｐ＜ ０．０５）、降低常氧大鼠肺动脉平均压（Ｐｐａ） （Ｐ＜ ０．０５） 和降低缺氧大鼠的Ｐｐａ和肺血管阻力（ＰＶＲ） （Ｐ＜ ０．０１）， 而且缺氧组大鼠下丘脑ＥＴ １ 及Ｐｐａ下降的幅度均显著大于常氧组大鼠， 尤以两组Ｐｐａ与ＰＶＲ降幅差最为显著 （Ｐ＜ ０．０１）。结果表明： ＥＴ １ 作为中枢神经介质， 参与肺血管张力的调节和缺氧性肺动脉高压的形成， ＥＴＡＳＯＤＮ颅内注射能舒张肺血管和降低肺动脉压， 有可能用于肺动脉高压的基因治疗

Effects of ET-1 Antisense on Pulmonary Hemodynamics in the Normoxic and Hypoxic Rats

Phosphorothioated antisense oligodeoxynucleotide(ASODN) targeted to preproendothelin1 was administered intracerebroventricularly in normoxic and hypoxic rats to develop a new way to prevent the process of hypoxic pulmonary arterial hypertension(HPAH) Following the administrtion of ETASODN, the changes of pulmonary hemodynamics and ET1 levels in specific brain regions were recorded, and the effects of ETASODN on ET1 levels were observed It was showed that the ET1 levels at hypothalamus in HPAH rats were higher than in normoxic ones;Injection of ETASODN decreased hypothalamus ET1 levels in normoxic and hypoxic rats, reduced pulmonary arterial mean pressure( pa) in normoxic rats, diminished pa and pulmonary vascular resistance(PVR) in hypoxic rats and the diminished amplitude of hypothalamus ET1 levels and pa in hypoxic rats were higher than in normoxic ones,especially the diminished amplitude of pa and PVR were much different between the two groups These results suggest that ET1, as a central neurotransmitter, participated in the regulation of pulmonary vascular tension and the development of HPAH in rats, and that intracranial injection of ETASODN could relax pulmonary vessels, decreas pa and might be a genic tool for treating HPAH