Baicalin Protects Rats With Pulmonary Hypertension Through PDGF/P38MAPK Signaling Pathway

ObjectiveTo investigate the protective effect and mechanism of Baicalin on monocrotaline(MCT)– induced pulmonary arterial hypertension in rats through p38MAPK/PDGF signaling pathway.MethodsIn vivo,forty SD rats were randomly divided into 4 groups: control group,pulmonary arterial hypertension group,baicalin 50 mg/kg group and baicalin100 mg/kg group.PAH model was established by a single intrabitoneal injection of MCT(60mg/kg).After the successful establishment of PAH,the rats were given baicalin(50 mg/kg and 100 mg/kg)by gavage for 28 days.Right ventricular catheter intubation was performed to determine right ventricular pressure(RVSP)and mean pulmonary artery pressure(m PAP).The contents of SOD,GSH-px,ICAM-1,VCAM-1,IL-8 and IL-1β in serum of rats were detected by ELISA,the formation of reactive oxygen species(ROS)in lung tissues was observed by dihydroethylingot(DHE)staining,and the protein expressions of bax and bcl-2 in lung tissues were detected by immunofluorescence.The protein expressions of P38 MAPK and PDGF were detected by immunoblotting.In vitro,human pulmonary artery endothelial cells(HPAECs)were cultured.HPAECs were treated with MCTP(60 μg/m L)for 24 h and baicalin(50、100 μmol/L)was treated for 24 h.The contents of SOD,GSH-px,ICAM-1,VCAM-1,IL-8 and IL-1β in the supernatant of HPAECs were detected by ELISA,and the formation of reactive oxygen species(ROS)in HPAECs was observed by DHE staining.The membrane potential level of HPAECs was detected by JC-1 staining.The protein expressions of P38 MAPK and PDGF were detected by immunofluorescence.ResultsIn vivo,compared with the control group,the levels of m PAP,RVSP,RVHI and W/D in model group were significantly increased,the levels of ICAM-1,VCAM-1,IL-8 and IL-1β in serum were significantly increased,but the activity of SOD and GSH-px in serum were significantly decreased,and the expression level of ROS in lung tissue was increased.The protein expression levels of bax,PDGF and P38 MAPK were significantly increased,while the protein expression level of bcl-2 was significantly decreased in model group.Compared with the model group,the levels of m PAP,RVSP,RVHI and W/D were significantly decreased,and the levels of ICAM-1,VCAM-1,IL-8 and IL-1β in serum were significantly decreased in baicalin group(50 mg/kg and100 mg/kg).However,SOD activity and GSH-px content in serum and were significantly increased,the level of ROS in lung tissue was decreased,protein expression levels of bax,PDGF and P38 MAPK were significantly decreased,and the protein expression level of bcl-2 was significantly increased in baicalin group.In vitro,compared with the control group,the levels of ICAM-1,VCAM-1,IL-8 and IL-1β in the supernatant of HPAECs in model group were significantly increased,and the protein expression levels of PDGF and P38 MAPK were significantly increased in model group,but the activity of SOD,the content of GSH-px and the level of membrane potential level in model group were significantly decreased,and the expression level of ROS in HPAECs in model group was increased.Compared with the model group,the levels of ICAM-1,VCAM-1,IL-8 and IL-1β in the supernatant of HPAECs in baicalin group were significantly decreased,and the protein expression levels of PDGF and P38 MAPK were significantly decreased in baicalin group,but the activity of SOD,the content of GSH-px and the level of membrane potential level in model group were significantly increased,and the expression level of ROS in HPAECs in baicalin group was decreased.Conclusions(1)Baicalin can improve the inflammatory response,oxidative stress and apoptosis of monocrotaline induced pulmonary hypertension rats.(2)Baicalin can improve the inflammatory response and oxidative stress activation of human pulmonary artery endothelial cells induced by Monocrotaline pyrrole.(3)Baicalin may play a role through PDGF/P38 MAPK signaling pathway.