循环微粒对大鼠肺动脉内皮的损害及与肺动脉高压的关系

Circulating particles effect of pulmonary hypertension through pulmonary artery endothelium function damage

目的:研究循环微粒(MPs)在肺动脉高压(PH)大鼠体内含量的改变及其与肺动脉高压的关系。方法:将48只雄性Wistar大鼠中30只随机分为对照组、MCT3组(M3组)、MCT5组(M5组)3组,每组10只。M3组、M5组用野百合碱一次性腹腔注射诱导PH模型,剩余的18只用于后续血管环检测。M3组和M5组分别在注射野百合碱后3周(中期)和5周(晚期)时右心导管法测定右心室收缩压(RVSP)来间接反映肺动脉压力,然后用腹主动脉采血法抽取大鼠血液并提取和检测MPs。用提取的三组MPs刺激大鼠肺动脉(每组6只)后检测内皮型一氧化氮合酶(eNOS)、弹性蛋白(elastin)蛋白的变化。结果:大鼠血浆MPs含量随PH病情进展而逐渐升高(M5>M3>C);MPs处理肺动脉后可下调eNOS表达,但是上调elastin表达,而且这一作用与PH病情相关,即M5作用强于M3(P<0.05)。结论:MPs随PH进展逐渐升高,升高的MPs可以损害内皮功能,这一发现进一步完善了PH的发病机制,为将来防治PH提供理论依据。

Objective：To investigate change of circulating microparticles（MPs）in pulmonary hypertension rats and its relationship with pulmonary hypertension.Methods：48healthy male Wistar rats were randomly divided into three groups.All rats except those in control group were injected intraperitoneally（ip）with a single dose（50mg/kg）of MCT to induce PH.Right ventricular systolic pressure（RVSP）was measured at 3and 5weeks before extracting rat blood from abdominal aortic for MPs detecting.Rat pulmonary artery（n=6）were stimulated with the extracted MPs,changes of endothelial nitric oxide synthase（eNOS）,elastin were detected.Results：Plasma MPs level in rats increased gradually with PH disease progression（M5〉 M3〉C）;MPs down-regulate eNOS,but up-regulate elastin expression in rat pulmonary artery,and this effect was related with PH progression.Conclusion：Plasma MPs level in rats increased gradually with PH disease progression,the increased MPs can impair endothelial function,this finding further perfects the mechanism of PH,and provide a theoretical basis for the future prevention and treatment of PH.