黄芩苷通过PDGF/P38 MAPK信号通路对肺动脉高压大鼠的保护作用

Protective effect of Baicalin on rats with pulmonary hypertension through PDGF/P38 MAPK signaling pathway

目的探讨黄芩苷对野百合碱诱导的肺动脉高压大鼠的保护作用和机制。方法40只SD大鼠随机分为4组:空白组、肺动脉高压模型组、黄芩苷50 mg/kg组、黄芩苷100 mg/kg组。通过单次腹腔注射野百合碱60 mg/kg建立肺动脉高压模型,黄芩苷连续灌胃28 d,右心室导管法测定右心室压力(right ventricular systolic pressures,RVSP)和平均肺动脉压(mean pulmonary artery pressure,mPAP);ELISA检测大鼠血清中总超氧化物歧化酶(superoxide dismutase,SOD)、GSH-px、细胞间粘附分子-1(intercellular cell adhesion molecule-1,ICAM-1)、血管细胞粘附分子-1(vascular cell adhesion molecule-1,VCAM-1)、IL-8和IL-1β含量;DHE染色观察大鼠肺组织活性氧(reactive oxygen species,ROS)形成情况;免疫荧光检测大鼠肺组织bax和bcl-2蛋白表达;免疫蛋白印迹检测P38 MAPK和血小板源生长因子(platelet-derived growth factor,PDGF)蛋白表达。结果与模型组比较,黄芩苷组大鼠mPAP、RVSP、RVHI和W/D显著降低,血清中ICAM-1、VCAM-1、IL-8和IL-1β蛋白含量显著减少,bcl-2蛋白含量、SOD活性和GSH-px含量显著升高,肺组织中ROS、bax、PDGF和P38 MAPK蛋白含量以及bax/bcl-2显著降低。结论黄芩苷可能通过PDGF/P38 MAPK信号通路改善肺动脉高压大鼠炎症、氧化应激和凋亡,从而发挥保护作用。

Objective To investigate the protective effect and mechanism of Baicalin on monocrotaline-induced pulmonary hypertension in rats.Methods Forty SD rats were randomly divided into 4 groups:a control group,a pulmonary hypertension group,a baicalin 50 mg·kg-1 group and a baicalin 100 mg·kg-1 group.A single intraperitoneal injection of monocrotaline(60mg/kg)was used to establish the pulmonary hypertension model.After injection of monocrotaline,baicalin was gavage continuously for 28 days.Right ventricular catheterization method was used to detect RVSP and mPAP.The levels of SOD,GSHpx,ICAM-1,VCAM-1,IL-8 and IL-1β in serum were detected by ELISA.The formation of reactive oxygen species(ROS)in lung tissue was observed by DHE staining.The expression of bax and bcl-2 in lung tissue were detected by immunofluorescence.Western blot was used to detect the protein expression of PDGF and P38 MAPK.Results Compared with the model group,mPAP,RVSP,RVHI and W/D were significantly decreased,and the contents of ICAM-1,VCAM-1,IL-8 and IL-1β in serum were significantly decreased,the contents of bcl-2,SOD and GSH-px were increased significantly in the Baicalin group.The contents of ROS,bax,PDGF and P38 MAPK and the level of bax/bcl-2 ratio in lung tissue were significantly decreased in the Baicalin group.Conclusions Baicalin may play a protective role in improving inflammation,oxidative stress and apoptosis of rats with pulmonary hypertension through PDGF/P38 MAPK signaling pathway.