黄芩苷通过抑制血管重构对实验性肺动脉高压的治疗作用研究（英文）

文献报道黄芩苷对肺动脉高压与右心室肥大具有抑制作用,但是作用机制尚不明确。最新研究显示, NF-κB与BMP信号通路在PAH中具有重要作用,NF-κB-BMP信号轴已经成为研究肺动脉高压血管重构发病机制的重要靶点。本研究目的是观察黄芩苷对实验性肺动脉高压血管重构的抑制作用以及对NF-κB-BMP信号轴的调控作用。结果显示黄芩苷能明显降低野百合诱导的肺动脉高压右心室收缩压与右心室肥厚指数,抑制肺动脉高压血管重构(P <0.05)。利用Western blot进行蛋白检测,结果显示BMPR2蛋白表达明显提高,而NF-κB p65、p-NF-κB p65、I-κBα与BMP抑制剂gremlin 1明显降低(P <0.05);免疫组织化学结果显示肺血管密度明显提高(P <0.05)。以上实验结果说明,黄芩苷对肺动脉高压肺脏和心脏损伤具有抑制作用是通过调控NF-κB-BMP信号通路,这将为防治肺动脉高压提供新的思路与方法。

Protective effect of baicalin on experimental pulmonary arterial hypertension through inhibition of pulmonary vascular remodeling

Previous studies have shown that baicalin can attenuate pulmonary arterial hypertension and right ventricular hypertrophy. However, the potential mechanism remains unexplored. Nuclear factor-κB (NF-κB) and bone morphogenetic protein (BMP) signaling pathway play an important role in monocrotaline (MCT) induced pulmonary arterial hypertension (PAH). Therefore, we aimed to observe the regulation of baicalin on the NF-κB-BMP axis and the subsequent anti-proliferation in pulmonary vascular. Our results showed that baicalin could significantly decrease right ventricular systolic pressure (RVSP) and the RV/left ventricle plus septum ratio (P < 0.05), and attenuate vascular remodeling. Furthermore, the result of westen blot showed that the protein expression level of BMP receptor 2 (BMPR2) was significantly increased, while NF-κB p65, p-NF-κB p65, inhibitor of NF-κB (I-κBα) and the BMP antagonist, gremlin 1 were significantly down-regulated in the baicalin group (P < 0.05). On the other hand, the result of immunohistochemical staining in lung showed that the capillary density of pulmonary arterioles significantly increased in the baicalin group compared with the MCT group (P < 0.05). We concluded thatbaicalin exerted the protective effects against the lung and heart damagethrough inhibiting NF-κB-BMP signaling pathway, providing new mechanistic information about PAH and right ventricular hypertrophy.