FHL1与COPD大鼠肺血管重塑的关系及其机制

Relationship between pulmonary vascular remodeling and FHL1 in rats with COPD and its mechanism

目的探讨FHL1与COPD大鼠肺血管重塑的关系及肺动脉平滑肌细胞增殖及表型转换在其中的作用。方法将20只雄性SD大鼠随机分为正常组及COPD组,每组10只。COPD组香烟烟雾暴露80 d复制COPD模型。图像分析法测定肺小动脉管壁厚度占外径的百分比(WT%)和管壁面积占血管总面积的百分比(WA%)。Western-blot法检测肺组织FHL1蛋白,荧光定量PCR法检测肺组织FHL1 mRNA。免疫组化法检测肺小动脉FHL1、α-actin及vimentin;PCNA法检测肺动脉平滑肌增殖细胞的阳性细胞率(PI);t检验及直线相关进行数据分析。结果 COPD组WT%和WA%较正常组升高(P<0.05),COPD组肺组织FHL1蛋白及mRNA(133.250±25.499和4.963±0.692)较正常组(51.188±18.259和1.697±0.360)升高(P<0.05)。COPD组肺小动脉FHL1、vimentin、α-actin及PI(0.316±0.093、0.085±0.030、0.219±0.049和0.575±0.076)较正常组(0.241±0.093、0.069±0.023、0.163±0.042和0.429±0.092)升高(P<0.05)。肺小动脉FHL1表达与WT%、WA%、vimentin及PI呈正相关(P<0.05),但肺小动脉FHL1表达与α-actin表达无相关性(P>0.05)。结论 COPD大鼠肺血管FHL1增加与肺血管重塑相关,FHL1可能通过增加肺血管平滑肌细胞增殖及促进平滑肌细胞合成表型转换参与COPD肺血管重塑。

Objective To evaluate the relationship of Four-and-a-half LIM domain 1 （ FHL1 ） and pulmonary artery remodeling in rats with chronic obstructive pulmonary disease（COPD） and to study the role of pulmonary artery smooth muscle cell proliferation and phenotype transformation in this course. Methods Twenty adult male SD rats were randomly divid- ed into two groups, one group（ 10 adult male rats） was exposed to air（ control group）and the other group （10 adult male rats） was exposed to cigarette smoke for 80 days （COPD group）. Image analysis was used to calculate the ratio of thick- ness/outside diameter of pulmonary arterioles（ WT% ） and the ratio of vessel wall area/total vessel area（ WA% ）. The levels of FHL1 and FHL1 mRNA in rat pulmonary were determined by Westeru-blot test and Real time fluorescent quantitative PCR. lmmunohistoehemistry was used to determine FHL1, α-actin and vimentin in pulmonary arterioles smooth muscle. PCNA was used to determine the proliferation level of pulmonary arterioles smooth muscle cell （ PI ）. The data were analyzed by T-test and linear correlation analysis. Results The WT% and WA% of COPD group were higher than control group（P 〈 0.05）. The levels of FHL1 and FHLlmRNA in pulmonary of COPD group （133. 250 25. 499 and 4.963 ± 0. 692） were higher than control group （51. 188 s 18. 259 and 1. 697 s 0.360） （ P 〈 0.05 ）. The levels of FHL1, vimentin,α-actin and PI on pulmonary arterioles of COPD group（0. 316 ± 0. 093,0. 085 ± 0. 030,0. 219± 0. 049 and 0.575 ± 0. 076 ） were higher than control group（0. 241 ±0. 093,0. 069 ±0. 023,0. 163 ±0. 042 and 0. 429 ±0. 092） （ P 〈 0.05 ）. The levels of FHL1 on pulmonary arterioles was positively related to WA% , WT% , vimentin and PI （ P 〈 0. 05 ）, but did not to α-actin. Conclusion The elevation of FHL1 level in pulmonary artery of COPD group is related to pulmonary artery remodeling. FHL1 may cause pulmonary artery remodeling by increasing proliferation of pulmonary arterioles smooth muscle cell and inducing the transformation of phenotype of pulmonary arteriole smooth muscle.