基于络病理论益气活血法调控Rho/ROCK通路对低氧性肺动脉高压大鼠血管重构影响

Effect of Regulating Rho/ROCK Pathway on Vascular Remodeling in Rats with Hypoxic Pulmonary Hypertension Based on Collateral Disease Theory and Supplementing Qi and Activating Blood Circulation

目的探讨益气活血法对低氧性肺动脉高压大鼠血管重构的影响及其作用机制。方法研究选用SD大鼠50只,随机分为空白组、模型组、中药组、西药组及结合组,每组10只。采用低氧法建立低氧性肺动脉高压大鼠模型。4周后测量各组大鼠平均肺动脉压力(mPAP);HE染色法观察各组大鼠肺小动脉病理形态;免疫组化测定肺小动脉PCNA的表达;ELISA法检测血清中P27^(kip1)的表达;Western Blot检测肺组织中RhoA、ROCK1的表达。结果与空白组比较,模型组mPAP明显升高(P<0.01);肺小动脉管壁明显增厚、管腔变窄;PCNA、P27^(kip1)、RhoA、ROCK1的表达显著增加(P<0.01)。与模型组比较,各药物治疗组mPAP显著降低(P<0.01);肺小动脉病理改变不同程度减轻;PCNA、P27^(kip1)、RhoA、ROCK1的表达显著降低(P<0.01)。中药组与西药组各指标未见明显差异。结合组各指标明显优于中药组及西药组。结论益气活血法中药能够参与调控Rho/Rock信号通路,改善肺小动脉血管重构,降低肺动脉压力。

Objective To investigate the effect of supplementing Qi and activating blood circulation on vascular remodeling in rats with hypoxic pulmonary hypertension and its mechanism.Methods 50SD rats were randomly divided into blank control group,model group,traditional Chinese medicine group,Western medicine group and combination group,with 10 rats in each group.Hypoxic pulmonary hypertension rat model was established by hypoxia method.After 4 weeks,the mean pulmonary artery pressure(mPAP)was measured;HE staining was used to observe the pathological morphology of pulmonary arterioles in each group;The expression of PCNA in pulmonary arterioles was measured by immunohistochemistry;The expression of p27^(kip1) in serum was detected by ELISA;Western blot was used to detect the expression of RhoA and Rock1 in lung tissue.Results Compared with the blank control group,mPAP in the model group was significantly higher(P<0.01);The wall of pulmonary arterioles became thicker and the lumen became narrower;The expressions of PCNA,p27^(kip1),RhoA and Rock1 increased significantly(P<0.01).Compared with the model group,mPAP in each drug treatment group decreased significantly(P<0.01);The pathological changes of pulmonary arterioles were alleviated in varying degrees;The expressions of PCNA,p27^(kip1),RhoA and Rock1decreased significantly(P<0.01).There was no significant difference between traditional Chinese medicine group and Western medicine group.The indexes of the combination group were significantly better than those of the traditional Chinese medicine group and the Western medicine group.Conclusion Traditional Chinese medicine of supplementing Qi and activating blood circulation can participate in regulating Rho/rock signal pathway,improve pulmonary arteriole vascular remodeling and reduce pulmonary artery pressure.