血府逐瘀汤对低氧性肺动脉高压大鼠肺血管重构及mTOR信号通路的影响

Effects of Xuefu Zhuyu Decoction on pulmonary vascular remodeling in hypoxic pulmonary hypertension rats and mTOR signaling pathway

目的:观察血府逐瘀汤对低氧性肺动脉高压(HPH)大鼠肺血管重构的干预作用及对mTOR信号通路的影响。方法:40只雄性SD大鼠随机分为正常对照组、模型组、血府逐瘀汤组、NVP-BEZ235组、药物联合组,每组8只。采用低压低氧法建立大鼠HPH模型。测定大鼠右心室压力(RVP)、平均肺动脉压(mPAP)和右心肥厚指数(RVHI),观察大鼠肺小动脉病理改变,免疫组化检测肺小动脉NF-κB表达,Western Blot检测肺组织mTOR信号通路蛋白和NF-κB表达。结果:与正常对照组比较,模型组大鼠RVP、mPAP、RVHI均显著升高(P<0.01),肺小动脉血管壁增厚、管腔变窄,p-mTOR、p-S6K、p-4E-BP1、NF-κB表达显著增加(P<0.05,P<0.01);与模型组比较,各药物治疗组大鼠RVP、mPAP、RVHI显著降低(P<0.05,P<0.01),肺小动脉病理改变不同程度减轻,p-mTOR、p-S6K、p-4E-BP1、NF-κB表达显著降低(P<0.05,P<0.01);与血府逐瘀汤组比较,药物联合组p-mTOR、p-S6K、p-4E-BP1表达显著降低(P<0.05)。结论:血府逐瘀汤能有效减轻HPH大鼠肺血管重构和右心肥厚,降低肺动脉压力,其机制可能与抑制mTOR信号通路和NF-κB活化相关。

Objective: To observe the effect of Xuefu Zhuyu Decoction on pulmonary vascular remodeling in hypoxic pulmonary hypertension(HPH) rats and its effect on the expression of mTOR signaling pathway. Methods: Forty male SD rats were randomized into normal control group, model group, Xuefu Zhuyu Decoction group, NVP-BEZ235 group, and drug combination group, with 8 rats in each group. The HPH rat model is established by using low pressure and low oxygen. Right ventricular pressure(RVP), mean pulmonary artery pressure(mPAP) and right ventricular hypertrophy index(RVHI) were measured. Pathological changes of pulmonary arterioles in rats were observed. The expression of NF-κB was detected by immunohistochemical method, and the expressions of mTOR signaling pathway protein and NF-κB were detected by Western Blot. Results: Compared with the normal control group, RVP, mPAP and RVHI were significantly increased(P<0.01) in the model group, with thickened pulmonary arterial wall and narrowed lumen, and increased expressions of p-mTOR, p-S6 K, p-4 E-BP1 and NF-κB(P<0.05, P<0.01). Compared with the model group, RVP, mPAP and RVHI were decreased in all drug treatment groups(P<0.05, P<0.01), pulmonary vascular remodeling was alleviated, and the expression of p-mTOR, p-S6 K, p-4 E-BP1 and NF-κB was decreased(P<0.05, P<0.01). Compared with Xuefu Zhuyu Decoction group, the expressions of p-mTOR, p-S6 K and p-4 E-BP1 were decreased(P<0.05) in drug combination group. Conclusion: Xuefu Zhuyu Decoction can reduce pulmonary artery pressure, alleviate pulmonary vascular remodeling and right heart hypertrophy in HPH rats. The mechanism may be related to inhibiting mTOR signaling pathway and NF-κB activation.