国际心血管病杂志2024,Vol.51Issue(3) :175-180.DOI:10.3969/j.issn.1673-6583.2024.03.013

紫草素调控白细胞介素-6治疗肺动脉高压的机制研究

Study on the mechanism of shikonin regulating interleukin-6 in the treatment of pulmonary arterial hypertension

王勋 左婉云 肖政辉 肖云彬 陈智 曾云红 李文凤 黄婷
国际心血管病杂志2024,Vol.51Issue(3) :175-180.DOI:10.3969/j.issn.1673-6583.2024.03.013

紫草素调控白细胞介素-6治疗肺动脉高压的机制研究

Study on the mechanism of shikonin regulating interleukin-6 in the treatment of pulmonary arterial hypertension

王勋 1左婉云 2肖政辉 3肖云彬 1陈智 1曾云红 1李文凤 4黄婷4
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作者信息

  • 1. 410071 长沙,湖南省儿童医院心血管内科
  • 2. 410011 长沙,中南大学湘雅二医院血液科
  • 3. 410071 长沙,湖南省儿童医院重症医学科
  • 4. 410071 长沙,湖南省儿童医院超声科
  • 折叠

摘要

目的:探讨紫草素通过抑制白细胞介素(IL)-6 及其下游信号通路逆转肺动脉高压(PAH)大鼠血流动力学和血管重构的机制.方法:24 只SD大鼠随机数字表法分为对照组(CON组)、野百合碱肺动脉高压组(MCT-PAH组)、肺动脉高压紫草素干预组(MCT-PAH+SH组),每组 8只.造模28 d后检测各组大鼠肺动脉血流动力学、右室肥厚指数,HE染色鉴定肺动脉形态学变化,Western blot和免疫组化检测IL-6、IL-21、CD163 等分子的表达及定位.结果:与CON组相比,MCT-PAH组大鼠肺动脉血流加速时间(PAAT)缩短,心脏右室内径(RVID)增宽,三尖瓣瓣环收缩期位移(TAPSE)减低,右室肥厚指数增加,右室收缩压(RVSP)升高,肺动脉血管壁明显增厚,且以中膜肥厚显著.与MCT-PAH组相比,MCT-PAH+SH组大鼠PAAT延长,RVID略减少,TAPSE增加,右室肥厚指数改善,RVSP降低且肺血管肥厚程度改善.免疫荧光结果显示MCT-PAH组大鼠肺小动脉中IL-6的表达水平较CON组升高,MCT-PAH+SH组较MCT-PAH组下降.Western blot结果显示MCT-PAH组大鼠肺组织IL-6、IL-21 表达水平较CON组增加,MCT-PAH+SH组较MCT-PAH组下降.MCT-PAH组大鼠肺血管壁CD163 表达水平较CON组明显升高,MCT-PAH+SH组较MCT-PAH组显著减低.结论:紫草素干预改善PAH大鼠右心血流动力学及肺血管重构,其机制可能与抑制IL-6及其下游分子IL-21、CD163 相关.

Abstract

Objective:Discuss whether shionin can reverse the changes of hemodynamic and vascular remodeling in animal models of PAH by regulating interleukin-6 and downstream signal pathways.Methods:Twenty-four SD rats were randomly divided into CON group,MCT-PAH group and MCT-PAH+SH group.Four weeks later,pulmonary artery hemodynamics,indexes related to right heart function and right ventricular hypertrophy index were detected.Morphological changes of pulmonary artery were identified by HE staining.IL-6 was detected by immunofluorescence.Western blot and immunohistochemistry techniques were performed to detect the expression of IL-6,IL-21 in rats'lung tissues and the expression and localization of CD163 in lung tissues.Results:Compared with CON group,pulmonary artery blood flow acceleration time(PAAT)was shortened,the inner diameter of the right ventricle(RVID)was widened,the tricuspid annular plane systolic excursion(TAPSE)was decreased,right ventricular hypertrophy index was increased,right ventricular systolic pressure(RVSP)was increased,pulmonary artery vascular wall was significantly thickened in MCT-PAH group,and the vascular remodeling was marked by middle membrane hypertrophy.These results indicated that the animal model of pulmonary artery hypertension was successfully established.After the intervention with shikonin,the above indexes had different changes.Immunofluorescence results showed that the expression of IL-6 in pulmonary arterioles of MCT-PAH group was higher than that of CON group,and the expression of IL-6 in pulmonary arterioles of shikonin group was lower than that of MCT-PAH group.The results of western blot showed that the expression of IL-6creased in MCT-PAH group.Shikonin treatment reduced expression of IL-6,IL-21 in PAH rat's lung.The expression of CD163 in pulmonary blood vessels were significantly increased in MCT-PAH group rats,but reduced after shikonin treatment.Conclusions:Shikonin treatment alleviated PAH via improving hemodynamics of right ventricle and pulmonary vascular remodeling in experimental PAH.The effect may be relative to inhibition of IL-6 and its downstream signal pathway activation.

关键词

肺动脉高压/紫草素/白细胞介素6

Key words

Pulmonary arterial hypertension/Shikonin/Interleukin-6

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基金项目

国家自然科学基金(81500041)

湖南省卫生健康委项目(20200849)

出版年

2024
国际心血管病杂志
上海市医学科学技术情报研究所

国际心血管病杂志

CSTPCD
影响因子:0.891
ISSN:1673-6583
参考文献量24
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