Protective effect and mechanism of nicorandil based on the BMP9/BMPR2/SMAD pathway against LPS-induced pulmonary microvascular endothelial cell injury
10.3969/j.issn.1671-8348.2025.09.007
- VernacularTitle:尼可地尔基于BMP9/BMPR2/SMAD通路对LPS诱导人肺微血管内皮细胞损伤的保护作用及机制
- Author:
Lei ZHOU
1
;
Changyu WU
;
Leiming TANG
Author Information
1. 浙江中医药大学,杭州 310000;舟山市妇女儿童医院急诊科,浙江舟山 316000
- Keywords:
nicorandil;
pulmonary microvascular endothelial cells;
oxidative injury;
inflammation;
BMP9/BMPR2/SMAD pathway
- From:
Chongqing Medicine
2025;54(9):2032-2040
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the protective effect and mechanism of nicorandil on lipopolysac-charide(LPS)-induced human microvascular endothelial cells(HPMVECs)injury based on BMP9/BMPR2/SMAD pathway and its mechanism.Methods The HPMVECs injury model induced by LPS(100 ng/mL)was established.The normal cultured HPMVECs were set as the NC group,and other model cells were set as the model group(LPS group),low,medium and high concentrations nicorandil groups(nicorandil 50,100,200μmol/L),si-NC+high nicorandil group,and si-BMP9+high nicorandil group.MTT assay was used to detect the cell proliferation activity;the apoptosis and intracellular ROS level were detected by flow cytometry;the levels of MDA,SOD and CAT in cells were detected by the micro assay;the levels of TNF-α,IL-6 and IL-1β in cells were detected by ELISA;the mRNA levels of BMP9,BMPR2 and SMAD1 were detected by RT-qPCR;and the expression of BMP9,BMPR2,SMAD1,Bcl-2,Bax proteins in cells was detected by Western blot.Re-sults Compared with the NC group,the proliferation activity of HPMVECs,SOD,CAT levels,Bcl-2 protein,BMP9,BMPR2,SMAD1 mRNA and protein expression levels in the LPS group were decreased(P＜0.05),the apoptosis rate and the Bax protein expression level,ROS,MDA,TNF-α,IL-6 and IL-1β levels were in-creased(P＜0.05).Compared with the LPS group,the proliferation activity of HPMVECs,SOD,CAT levels,Bcl-2 protein level,BMP9,BMPR2,SMAD1 mRNA and protein expression levels in the low,middle and high concentrations nicorandil groups were increased,the apoptosis rate and the Bax protein level,ROS,MDA,TNF-α,IL-6 and IL-1β levels were decreased obviously(P＜0.05);compared with the high concentration nic-orandil group,the si-BMP9+high nicorandil group and LPS group showed the same trend,si-BMP9 was able to reverse the protective effect of high nicorandil group on LPS induced HPMVECs injury to some extent.Conclusion Nicorandil could reduce the oxidative stress,inflammatory reaction and cell apoptosis induced by LPS in HPMVECs and inhibit LPS induced HPMVECs injury by up-regulating the expression of BMP9/BM-PR2/SMAD pathway.
