通心络对低压低氧性肺动脉高压大鼠HIF-1α及相关因子的作用∗

摘要

目的：：探讨通心络对低压低氧性肺动脉高压大鼠缺氧诱导因子-1α(HIF-1α)及相关因子的影响。方法：30只体重200-250g的 SD雄性大鼠,随机分为常压常氧对照组(对照组)、低压低氧模型组(模型组)、低压低氧+通心络干预组(通心络干预组),每组10只。采用低压低氧舱模拟海拔5000m的高原环境(大气压50kp,氧浓度10%)。模型组和通心络干预组大鼠每日入舱8h,其余时间为常压常氧环境。通心络干预组每天入舱前给予通心络1.2 g生药/kg灌胃1次,对照组于同一实验室的常压常氧环境中饲养。4周后比较各组大鼠平均肺动脉压(mPAP)、右心室(RV)肥厚指数以及血清 HIF-1α、血管内皮生长因子(VEGF)、内皮素-1(ET-1)等因子水平。结果：4周后,与对照组相比,模型组大鼠mPAP、RV 肥厚指数及 HIF-1α、VEGF、ET-1等因子水平显著升高(P<0.05)。与模型组相比,通心络干预组大鼠mPAP、RV肥厚指数及血清 HIF-1α、VEGF、ET-1等因子水平均显著降低(P<0.05),且 RV肥厚指数及血清 HIF-1α、ET-1水平与对照组水平差异无统计学意义(P>0.05)。结论：通心络可能通过降低 HIF-1α水平等干预低压低氧性肺动脉高压的发生发展。%Objective:To study the effect of Tongxinluo on HIF-1αin rats with hypobaric and hypoxia pulmo-nary hypertension.Method:30 male SD rats weighing 200-250g were randomly divided into three groups:control group with normal pressure and normal oxygen(control group),pulmonary hypertension group with low-pressure and low-oxygen (model group),and the group treated by Tongxinluo in low-pressure and low-oxygen condition (Tongxinluo intervention group).Each group included 10 rats.Auto-modulating hypobaric and hypoxic cabin was used to simulate 5000m high altitude environment (air pressure 50kpa,oxygen concentration 10%).Tongxinluo (1. 2g/kg crude drug)was given by gastrogavage to rats in Tongxinluo intervention group once daily.Control group were exposed to normal-pressure and normal-oxygen in the same laboratory environment.4 weeks later,the mean pulmonary arterial pressure (mPAP)and right ventricular (RV)mass index were measured.Concentrations of HIF-1α,VEGF and ET-1 in blood were detected.Results:Compared with control group,mPAP,RV mass index and thelevels of HIF-1α,VEGF,ET-1 in model group were significantly increased (P<0.05).Compared with model group,rats of Tongxinluo intervention group showed lower mPAP and RV mass index,and the levels of HIF-1α, VEGF and ET-1 decreased remarkably (P<0.05).There was no significant difference between control group and Tongxinluo intervention group in right ventricular hypertrophy index and the levels of serum HIF-1αand ET-1 (P>0.05).Conclusion:Tongxinluo may influence the occurrence and development of hypobaric and hypoxia pulmonary hypertension by downregulated the level of HIF-1α.