间歇性低压低氧对大鼠肺动脉高压的 预防作用及血管保护机制

Preventive effect of intermittent hypobaric hypoxia on pulmonary hypertension in rats and vascular protective mechanisms

摘要:

目的 采用野百合碱（MCT）诱导雄性SD 大鼠肺动脉高压（PAH）模型，观察间歇性低压低氧（IHH） 对动物模型PAH 的预防作用及其对肺血管的保护机制。方法 大鼠随机分为正常对照组（CON 组）、肺动 脉高压组（PAH 组）、间歇性低压低氧组（IHH 组）和IHH+MCT 组。CON 组不进行任何处理，28 d 后直 接行右心室收缩压（RVSP）和肺动脉平均压（mPAP）的测定，计算右心室肥厚指数（RVHI）并行血管环 灌流实验观察血管反应性改变。PAH 组经腹腔注射MCT 14 d 后进行实验。IHH 组接受模拟5 km 海拔高 度，6 h/d 的IHH 处理28 d 后实验。IHH+MCT 组先经受28 d 的IHH 后，腹腔注射MCT 14 d 后实验。结果 PAH 组大鼠从注射MCT 后1 周体重较CON 组减轻，倦卧，喘促，活动量、进食量减少。IHH+MCT 组大 鼠一般情况较同期的PAH 组有所改善，但较CON 组差。实验过程中PAH 组死亡2 只，其余各组均全部存 活。PAH 组的mPAP、RVSP、RV、LV+S、RVHI 与其他组比较，差异有统计学意义（P <0.05），PAH 组高 于其他组，IHH+MCT 组的指标较PAH 组显著降低。PAH 组大鼠肺动脉的内皮依赖性血管收缩及舒张反应 与CON 组比较，差异有统计学意义（P <0.05），PAH 组受损，而IHH 干预后，可改善其受损的内皮依赖性的 血管收缩及舒张反应。结论 IHH 能够有效降低MCT 诱导的PAH 大鼠升高的mPAP、RVSP、RV、LV+S、 RVHI，且对PAH 大鼠肺血管的内皮依赖性血管收缩及舒张反应具有保护作用。

Abstract:

Objective To observe the effect of intermittent hypobaric hypoxia (IHH) on function and morphology of rat pulmonary vessels and explore its protection mechanisms. Methods Male SD rats were randomly divided into 4 groups including a CON group, a PAH group, an IHH group, and an IHH+MCT group. The rats in the CON group did not have any treatment. After normal feeding for 28 days, right ventricular systolic pressure (RVSP) and pulmonary artery pressure (PAP) were tested directly, right vetricular hypertrophy index (RVHI) was calculated and the changes of vascular reactivity were observed in vascular ring perfusion experiment. In the PAH group the indexes were measured 14 days after injection of monocrotaline (MCT). The rats in the IHH group were tested after IHH treatment for 28 days. The rats in the IHH+MCT group were subjected to 28-day IHH first and then injection of MCT, the indexes were tested 14 days after injection. Results The rats in the PAH group had reduced weight, activity levels and food intake, tired lying, breathlessness 1 week after injection of MCT compared to the control group. In the PAH group 2 rats died during the experiment, the remaining rats were all survived. The indexes in the IHH+MCT group were improved compared to those in the PAH group in the same period, but worse than those in the CON group. RVSP, mPAP, RV, LV+S and RVHI in the PAH group were significantly higher than those in the remaining three groups (P < 0.05). Endothelium-dependent contractile and vasodilation of pulmonary artery in the PAH group induced by MCT were significantly impaired as compared to the CON group (P < 0.05), however, IHH intervention could significantly improved them (P < 0.05). Conclusions IHH can effectively reduce the elevated mPAP, RVSP, RV, LV+S and RVHI in the rats with pulmonary hypertension induced by MCT. IHH has protective effect on endothelium-dependent contractile and vasodilation response in pulmonary vessels of the rats with pulmonary hypertension.