中国药理学与毒理学杂志2025,Vol.39Issue(11):821-828,8.DOI:10.3867/j.issn.1000-3002.2025.08285
松果菊苷对野百合碱诱导大鼠肺动脉高压的改善作用及机制
Effects of echinacoside on monocrotaline-induced pulmonary arterial hypertension model rats by regulating CaM and TRPC1/4/6 protein
摘要
Abstract
OBJECTIVE To investigate the effect and mechanism of echinacoside(ECH)on mono-crotaline-induced pulmonary arterial hypertension(PAH)in rats.METHODS ① In vivo,SD rats were randomly divided into the normal control group,PAH group,model+ECH 15 mg·kg-1 group,model+ECH 30 mg·kg-1 group and model+aspirin 8 mg·kg-1 group.On the first day,a PAH rat model was established via intraperitoneal injection of 40 mg·kg-1 of monocrotaline.The normal control group was given the same volume of normal saline by intraperitoneal injection.The treatment started on the second day after modeling,once a day,for 28 d.The mean pulmonary artery pressure(mPAP)was measured via right cardiac catheterization and the degree of right ventricular hypertrophy was measured by weighing.Pulmonary artery remodeling was observed using HE staining.The protein expression levels of calmodulin(CaM),transient receptor potential channel 1(TRPC1),TRPC4,and TRPC6 were detected by Western blotting.②In vitro,pulmonary artery smooth muscle cells(PASMCs)of rats were randomly divided into the cell control group,noradrenaline(NE)group,NE+ECH 400 μmol·L-1 group and NE+ECH 450 μmol·L-1 group.Each group was pre-incubated with the corresponding concentration of ECH for 20 min,followed by the addition of 1 μmol·L-1 NE,and then cultured for 24 h.The protein expression levels of CaM,TRPC1,TRPC4,and TRPC6 were detected by Western blotting.RESULTS ① In vivo,compared with the normal control group,the right cardiac hypertrophy index and mPAP of the PAH group were significantly increased,the pulmonary vascular wall was thickened,and the expressions of CaM,TRPC1,TRPC4 and TRPC6 proteins were significantly increased.After ECH 30 mg·kg-1 treatment of monocrotaline-induced PAH rats,the right cardiac hypertrophy index and mPAP were significantly decreased,and the expressions of CaM,TRPC1,TRPC4 and TRPC6 proteins were significantly down-regulated.The pulmonary artery remodeling in PAH rats treated with ECH 15 and ECH 30 mg·kg-1 was improved.② In vitro,compared with cell control group,the expressions of CaM,TRPC1,TRPC4 and TRPC6 in PASMCs of the NE group were upregulated.Compared with the NE group,the expressions of CaM,TRPC1,TRPC4 and TRPC6 in PASMCs were significantly decreased.CONCLUSION ECH may inhibit the expressions of CaM,TRPC1,TRPC4 and TRPC6 proteins,thus improving pulmonary vascular contraction and pulmonary artery remodeling,and alleviating PAH.关键词
松果菊苷/瞬时受体电位通道/钙调蛋白/平滑肌细胞/肺动脉高压Key words
echinacoside/transient receptor potential channel/calmodulin/smooth muscle cell/pulmonary arterial hypertension分类
医药卫生引用本文复制引用
赵悦孚,王金宇,夏晴晴,孙浩田,雷皋翔,赵恩麒,毕宏涛,盖祥云..松果菊苷对野百合碱诱导大鼠肺动脉高压的改善作用及机制[J].中国药理学与毒理学杂志,2025,39(11):821-828,8.基金项目
青海省2025年中央引导地方科技发展资金计划项目(2025-ZY-047) (2025-ZY-047)
青海省基础研究计划应用基础研究(2020-ZJ-703) (2020-ZJ-703)
青海省昆仑英才·高端创新创业人才项目(2020) Central Government's Funding Plan for Guiding Local Scientific and Technological Development in Qinghai Province in 2025(2025-ZY-047) (2020)
Application Basic Research of Foundation Research Project in Qinghai Province(2020-ZJ-703) (2020-ZJ-703)
and Kunlun Talents and High-level Innovative Entrepreneurship Program of Qinghai Province(2020) (2020)