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MCTPAH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。
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,MCTPAH 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 MCTPAH 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.
作者
王勋
左婉云
肖政辉
肖云彬
陈智
曾云红
李文凤
黄婷
WANG Xun;ZUO Wanyun;XIAO Zhenghui;XIAO Yunbin;CHEN Zhi;ZENG Yunhong;LI Wenfeng;HUANG Ting(Department of Cardiology,Hunan Children's Hospital,Changsha 410071;Department of Hematology,The Second Xiangya Hospital,Central South University,Changsha 410011;Department of Intensive Care Unit,Hunan Children's Hospital,Changsha 410071;Department of Ultrasound,Hunan Children's Hospital,Changsha 410071,China)
出处
《国际心血管病杂志》
2024年第3期175-180,共6页
International Journal of Cardiovascular Disease
基金
国家自然科学基金(81500041)
湖南省卫生健康委课题(20200849)。
关键词
肺动脉高压
紫草素
白细胞介素6
Pulmonary arterial hypertension
Shikonin
Interleukin-6
作者简介
通信作者:肖云彬,E-mail:xiaoyunbinrui@126.com。
