缺氧(环境)
肺动脉高压
药理学
肺动脉
生发中心
西地那非
胚胎血管重塑
细胞
医学
内科学
免疫学
化学
B细胞
抗体
有机化学
氧气
生物化学
作者
Cheng Li,Hao Zhu,Shaoze Zhang,Fang Meng,San Li,Guang Li,Jun Zha,Shangjie Wu,Li Zhu,Aiguo Dai
出处
期刊:Phytomedicine
[Elsevier]
日期:2022-05-23
卷期号:102: 154171-154171
被引量:10
标识
DOI:10.1016/j.phymed.2022.154171
摘要
Pulmonary hypertension (PH) is a progressive disorder lacking a validated and effective therapy which characterized by elevated pulmonary arterial pressure, vascular remodeling and eventual death. FDA approved sildenafil is being used as a first-line drug for PH, however, neither survival rates nor quality of life have been improved because of side effects and patient noncompliance. Thus, the exploration of novel therapeutic drugs is urgently needed. Astragaloside IV (ASIV) exhibits a protective effect on HPH, but its mechanisms of action is unclear.CD4+T cell subsets, Tfh and Tfr cells, may contribute to the development of chronic hypoxia-induced PH (HPH). We hypothesized that ASIV could effectively ameliorates pulmonary vascular remodeling of HPH by restraining the Tfh cell response and expanding Tfr cell response.HPH mice model was established by exposure to chronic hypoxia for 21 days. Mice were randomly assigned to six groups: NaCl group, model group, SN group (100 mg/kg of sildenafil), low-dose group (20 mg/kg of ASIV), medium-dose group (40 mg/kg of ASIV) and high-dose group (80 mg/kg of ASIV). Primary culture and identification of distal pulmonary artery smooth muscle cells (PASMCs) in mice were established. Here, we demonstrated that ASIV treatment could significantly ameliorate the increase of mean PAP, RV/ (LV+S) ratio and PAMT in HPH mice. ASIV inhibited Tfh cell differentiation and IL-21 production, but promoted Tfr cell differentiation and TGF-β, IL-10 production. Chronic hypoxia promoted germinal center B cell responses, which inhibited by ASIV. ASIV regulated Tfh and Tfr cell differentiation by inhibiting the phosphorylation of mTOR signaling pathway, and the effect of ASIV-H was better than that observed in the SN group. ASIV inhibited the proliferation, migration and adhesion of PASMCs in vitro. Moreover, ASIV significantly downregulated the protein level of RhoA and upregulated the protein level of p27 in PASMCs under hypoxic condition.Collectively, ASIV may regulate Tfh and Tfr cell responses to subsequently repress pulmonary vascular remodeling and hypoxic pulmonary hypertension.
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