血府逐瘀汤通过PI3K/AKT/mTOR信号通路影响低氧性肺动脉高压大鼠肺血管重构的研究

Study on Effect of Xuefu Zhuyu Decoction on Pulmonary Vascular Remodeling in Hypoxic Pulmonary Hypertension Rats Via PI3K/AKT/mTOR Signaling Pathway

关键词:  血府逐瘀汤  低氧性肺动脉高压  肺血管重构  PI3K/AKT/mTOR信号通路  增殖细胞核抗原

Key words:  Xuefu Zhuyu decoction  hypoxic pulmonary hypertension  pulmonary vascular remodeling  PI3K/AKT/mTOR signaling pathway  proliferating cell nuclear antigen

摘要:

目的 探讨血府逐瘀汤对低氧性肺动脉高压（hypoxic pulmonary hypertension，HPH）大鼠肺血管重构的影响及其相关机制。方法 40只♂ 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。HE染色观察大鼠肺小动脉病理改变，Masson染色观察肺小动脉胶原纤维含量，免疫组化检测肺小动脉增殖细胞核抗原（proliferating cell nuclear antigen，PCNA）的表达，Western blotting测定肺组织p-AKT、AKT、p-mTOR、mTOR和PCNA的表达。结果 与正常对照组比较，模型组大鼠肺小动脉血管壁增厚、管腔变窄，胶原纤维含量显著增加（P<0.01），PCNA、p-AKT、p-mTOR表达增加（P<0.05或P<0.01）；与模型组比较，各药物治疗组大鼠肺小动脉病理改变不同程度减轻，胶原纤维含量显著减少（P<0.01），PCNA、p-AKT、p-mTOR表达降低（P<0.05或P<0.01）；药物联合组与血府逐瘀汤组相比，胶原纤维含量减少（P<0.05），PCNA、p-AKT、p-mTOR表达降低（P<0.01）。结论 血府逐瘀汤能有效减轻HPH大鼠肺血管重构，减少血管壁胶原纤维含量以及PCNA的表达，其机制可能与抑制PI3K/AKT/mTOR信号通路活化相关。

Abstract:

OBJECTIVE To explore the effect of Xuefu Zhuyu decoction on pulmonary vascular remodeling in hypoxic pulmonary hypertension(HPH) rats and its related mechanism. METHODS Forty ♂ SD rats were randomly divided 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 was established by using low pressure and low oxygen. Pathological changes of pulmonary arterioles were observed by HE staining. The content of collagen fibers in pulmonary arterioles was measured by Masson staining. The expression of proliferating cell nuclear antigen(PCNA) was detected by immunohistochemical method, and the expressions of p-AKT, AKT, p-mTOR, mTOR and PCNA were detected by Western blotting. RESULTS Compared with normal control group, the walls of pulmonary arterioles thickened with the lumen narrowed in model group. The content of collagen fibers and the expressions of PCNA, p-AKT, p-mTOR were increased(P<0.05 or P<0.01). Compared with model group, in all treatment groups, pulmonary vascular remodeling was alleviated in varying degrees, the content of collagen fibers significantly reduced(P<0.01), and the expressions of PCNA, p-AKT, p-mTOR were decreased(P<0.05 or P<0.01). Compared with Xuefu Zhuyu decoction group, the content of collagen fibers reduced(P<0.05) and the expressions of PCNA, p-AKT, p-mTOR were decreased(P<0.01) in drug combination group. CONCLUSION Xuefu Zhuyu decoction can alleviate pulmonary vascular remodeling in HPH rats, decrease the content of collagen fibers in pulmonary arterioles and the expression of PCNA. The mechanism may be relevant to inhibiting PI3K/AKT/mTOR signaling pathway.