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|本期目录/Table of Contents|

法舒地尔改善低氧致肺动脉血管重构的实验研究

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2015年第5期
页码:
535-539
栏目:
基础研究
出版日期:
2015-05-05

文章信息/Info

Title:
Fasudil improves hypoxia-induced remodeling of pulmonary artery in mice
作者:
刘 蕾; 沈 歆; 夏 玉; 陈 周; 张志武; 李小强
(第四军医大学药学院药理学教研室，陕西 西安 710032)
Author(s):
LIU Lei;  SHEN Xin;  XIA Yu;  CHEN Zhou;  ZHANG Zhi-wu;  LI Xiao-qiang
(Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
法舒地尔; 低氧; 肺动脉; 重构
Keywords:
fasudil;  hypoxia;  pulmonary artery;  remodeling
分类号:
R543.2
DOI:
-
文献标识码:
A
摘要:
目的 观察法舒地尔(fasudil)对慢性低氧引起的肺动脉血管重构的作用，进而探讨其可能的机制。方法 建立小鼠低氧损伤模型。实验分为对照组、低氧组和法舒地尔组〔15 mg/(kg·d),腹腔注射〕。采用HE染色观察法舒地尔对低氧致小鼠肺动脉血管重构的作用和影响；应用蛋白质印迹法检测法舒地尔对经典瞬时受体电位通道1（TRPC1）表达的影响；分离消化肺动脉平滑肌细胞，采用双波长离子影像技术测定法舒地尔对TRPC1介导的肺动脉平滑肌细胞全细胞钙变化的影响。结果 组织形态学观察发现，与对照组相比，长期慢性低氧可致小鼠肺动脉血管壁和心脏右室壁明显增厚，肺动脉血管TRPC1蛋白表达显著增加（P<0.05），这些变化可被法舒地尔显著降低（P<0.05）；与正常组比较，环匹阿尼酸（CPA）诱导低氧组肺动脉平滑肌细胞胞内自由钙离子浓度（［Ca2+］i）显著升高（P<0.05）；而CPA诱导的法舒地尔组肺动脉平滑肌细胞［Ca2+］i升高显著降低（P<0.05）。结论 法舒地尔可显著抑制慢性低氧引起的肺动脉血管重构，其机制可能与法舒地尔抑制TRPC1蛋白表达，进而减弱由TRPC1介导的细胞Ca2+动员密切相关。
Abstract:
AIM To investigate the effect of fasudil on hypoxia-induced remodeling of pulmonary artery and its mechanism. METHODS Hypoxia-induced remodeling model of pulmonary artery were made in BALB/c mice. Mice were divided into three groups: control group, hypoxic group and fasudil group ［15 mg/(kg·day)］, intraperitoneal injection). Hemodynamic measurements and histological studies were performed to detect pulmonary artery remodeling. Expression of canonical transient receptor potential channel 1 (TRPC1) was detected using Western blot and intracellular free calcium concentration (［Ca2+］i) was measured using a fluorescence imaging system. RESULTS Histomorphologic observation showed that chronic hypoxia obviously induced pulmonary artery remodeling, right ventricular wall thickening and higher expression of TRPC1 compared with control group. After treatment with Rho-kinase (ROCK) inhibitor fasudil, hypoxia-induced remodeling in pulmonary artery and right ventricular significantly were inhibited (P<0.05) and the expression of TRPC1 was dramatically decreased (P<0.05). Ca2+ influx in pulmonary artery smooth muscle cells elicited by store depletion using cyclopiazonic acid (CPA) was dramatically augmented in hypoxia group (P<0.05). However, fasudil obviously attenuated this change (P<0.05). CONCLUSION Inhibition of ROCK by fasudil can significantly attenuate hypoxia-induced increase of TRPC1 expression in pulmonary artery and alleviate Ca2+ influx through TRPC1 channel elicited by CPA, which might contribute to hypoxia-induced pulmonary artery remodeling.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2015-01-19.
基金项目：国家自然科学基金项目资助（81170107；30800433）
通讯作者：李小强，副教授，主要从事心血管药理学研究 Email：xxqqli@fmmu.edu.cn
作者简介：刘蕾，硕士生 Email：2271385707@qq.com
更新日期/Last Update: 2015-04-28