波生坦抑制低氧介导的大鼠肺动脉中5-羟色胺转运体的过度表达

Bosentan reduces the hypoxia-induced over-expression of the serotonin transporter in pulmonary arteries in rats

目的 观察5-羟色胺转运体（5-HTT）在低氧性肺动脉高压（HPH）大鼠肺动脉中的表达,探讨波生坦对其肺动脉中5-HTT表达的影响.方法 30只雄性SD大鼠随机分为对照组（C组）、低氧组（H组）和波生坦组（B组）（每组10只）.C组于正常环境中饲养3周,其余2组置于低压低氧舱中饲养3周.B组大鼠予以波生坦100mg·kg^-1·d^-1灌胃,H组按体质量同体积蒸馏水灌胃.测定各组大鼠的平均肺动脉压力（mPAP）、右心室收缩压（RVSP）.免疫组织化学和Western-blot方法分别观察和测定大鼠肺动脉和肺组织中5-HTT的表达水平.结果 H组大鼠的mPAP和RVSP明显高于C组（P值均＜0.05）;和H组大鼠相比,B组大鼠mPAP和RVSP均显著降低（P值均＜0.05）.免疫组织化学和Western-blot结果显示：和C组相比,H组大鼠肺动脉和肺组织中5-HTT的表达明显升高,而B组大鼠肺动脉和肺组织中5-HTT的表达明显低于H组.结论 HPH大鼠肺动脉和肺组织中5-HTT呈过表达,而波生坦可以显著抑制低氧介导的大鼠肺动脉和肺组织中5-HTT的表达增多,这可能是波生坦的新的药理机制之一.

Objective To observe the effect of bosentan on the expression of serotonin transporter in the pulmonary arteries of hypoxia-induced pulmonary hypertension （HPH）rats.Methods Thirty male Sprague-Dawley rats were randomly divided into 3 groups：control group,hypoxia group and bosentan group.The rats in control group stayed in orthobaric environment.The rats in experimental groups had been kept in hypobaric chamber for 3 weeks.In hypoxia group and bosentan group,the sodium chloride or bosentan was administrated by lavage in hypobaric chamber.The mean pulmonary arterial pressure （mPAP） and right ventricular systolic pressure （RVSP） were measured.The immunohistochemistry and Western-blot were used to observe the expressions of serotonin transporter in pulmonary tissues of each group rats.Results Compared with control group,the levels of mPAP and RVSP in placebo group increased significantly.Bosentan group showed a significant decrease in mPAP and RVSP,which were not significantly different with those in normoxic group.Immunohistochemistry and Western-blot shows that the expression of 5-HTT in the pulmonary arteries and lung tissues of hypoxia group rats increased significantly compared with control group.However,compared with hypoxia group,the expression of 5-HTT in the pulmonary arteries and lung tissues of bosentan group rats was lower significantly.Conclusions Bosentan decreases the expression of 5-HTT in the pulmonary arteries and lung tissues of HPH rats,which may be a new mechanism in its therapy of chronic HPH.