基于MicroRNA-130a靶向调节Gax的表达探讨通阳宣痹方对肺动脉高压血管重构的作用

The main reason of pulmonary arterial hypertension (PAH) is vascular remodeling-induced vascular stenosis. Proliferation of vascular smooth muscle cells (VSMCs) is essential foe vascular remodeling. MicroRNA-130a (miR-130a) is involved in proliferation of VSMCs, and it maybe regarded as the focus of vascular remodeling. Compound macrostem onion capsule was meticulous developed on the basis of Zhangzhongjing’s ancient formula and has been patented.Study about the relation between the expression of miR-130a and compound macrostem onion capsule has not yet to see. This project intends to explore these questions in two types PAH rat model induced by hypoxia and monocrotaline, and appraised the effect of compound macrostem onion capsule on the expression of miR-130a. Rat primary VSMCs was created under hypoxia. The mimic of miR-130a was used to overexpress miR-130a, and down-regulation of miR-130a was was used to miR-130a inhibitor. To evaluate the effect of compound macrostem onion capsule on the expression of miR-130a, and explore the role and mechanism of miR-130a in the proliferation of VSMCs. This study will provide the theoretical and experimental basis for compound macrostem onion capsule using in clinical treating PAH.

肺动脉高压（PAH）的主要原因是血管重构引起的血管狭窄，抑制平滑肌细胞增殖是改善血管重构的关键。MicroRNA-130a(miR-130a)参与PAH肺动脉平滑肌增殖，miR-130a有可能是研究肺动脉高压血管重构的重点。通阳宣痹代表方—复方薤白胶囊是本课题组根据汉代张仲景古方化载研制而成，并取得专利。目前尚未见miR-130a与复方薤白胶囊降低肺动脉高压，改善血管重构关系的相关报道。所以本课题拟以野百合碱和低氧诱导的PAH大鼠为体内模型，观察复方薤白胶囊对肺动脉miR-130a的影响；建立低氧大鼠原代肺动脉平滑肌细胞（VSMCs）模型，并在细胞中观察miR-130a-Gax通路，评价复方薤白胶囊对VSMCs中miR-130a-Gax的影响，为通阳宣痹方—复方薤白胶囊的临床应用治疗PAH提供实验和理论依据。

肺动脉高压 ( Pulmonary arterial hypertension , PAH ) 是一种以持续肺动脉压增高为特征的进行性肺血管疾病，导致肺血管阻力增加。肺动脉高压的主要原因是血管重构引起的血管狭窄，平滑肌增殖在这一过程发挥重要作用，抑制平滑肌细胞增殖是改善血管重构的关键。MicroRNA-130a (miR-130a) 及Gax参与了PAH肺动脉平滑肌增，miR-130a及Gax有可能是研究肺动脉高压血管重构的重点，也启发我们设计了本课题。通阳宣痹代表方——复方薤白胶囊，是根据汉代张仲景古方化载研制而成，并取得专利，广泛用于临床心肺疾病的治疗，临床运用已有二十余年。本课题拟以野百合碱诱导的肺动脉高压大鼠为动物模型，观察复方薤白胶囊对肺动脉高压大鼠肺血管重构及肺动脉miR-130a的影响；建立低氧大鼠原代肺动脉平滑肌细胞(PASMCs)模型，采用并在细胞实验中观察miR-130a-Gax通路，评价复方薤白胶囊对PASMCs中miR-130a-Gax的影响，为通阳宣痹方——复方薤白胶囊的临床应用治疗PAH提供实验和理论依据。本研究发现，复方薤白胶囊对于PAH大鼠治疗有效，可以改善其临床症状，降低肺动脉压、改善肺血管重构，降低miR-130a 的表达并升高 Gax的表达。复方薤白胶囊对于低氧培养的 PASMCs 细胞具有改善增殖、改善细胞周期、促进凋亡的作用，可以降低 miR-130a 表达水平，升高 Gax 的表达水平。复方薤白胶通过干预 miR-130a 靶向调控 Gax，抑制肺动脉平滑肌细胞的增殖，达到改善肺血管重构、降低肺动脉高压的作用。本研究对防治肺动脉高压具有重要意义，提供新思路新靶点。