低氧诱导成肌纤维细胞形成在低氧性肺血管重塑中的作用  

The role of hypoxia-induced myofibroblast formation in hypoxic pulmonary vascular remodeling

作　　者：李柏完[1] 蒋永亮 戴爱国 

机构地区：[1]南华大学附属第三医院呼吸疾病研究室,湖南省衡阳市421900 [2]湖南省老年医院,湖南省老年医学研究所呼吸疾病研究室,长沙市410001

出　　处：《实用医学杂志》2007年第10期1455-1457,共3页The Journal of Practical Medicine

基　　金：湖南省医药卫生科研基金(编号:02-Y081);湖南省教育厅科研基金(编号:03C397);湖南省医药卫生科研基金(编号:B2004-137)资助项目

摘　　要：目的:探讨低氧性肺动脉高压(HPH)无肌性肺动脉肌化的细胞来源。方法:雄性Wistar大鼠40只,分为对照组和低氧3、7、14、21d组,每组8只,低氧组复制HPH大鼠模型。测定各组平均肺动脉压(mPAP),右心室肥大指数(RVHI),肺小动脉病理及其形态计量学;细胞培养实验观察人胚肺成纤维细胞表型转化,透射电镜观察微血管的超微结构改变。结果:(1)低氧7d起大鼠mPAP、管壁面积/管总面积、管腔面积/管总面积分别为(18.41±0.37)mmHg、(52.2±0.8)%、(47.8±0.8)%与对照组(14.02±0.41)mmHg、(64.5±1.3)%、(35.5±1.3)%比较差异有显著性(P<0.05),低氧14d起稳定于高水平;低氧14d RVHI为(25.0±1.8)%,与对照组(23.6±0.5)%比较差异也有显著性(P<0.05)。(2)细胞培养显示低氧72h部分人胚肺成纤维细胞表达α-平滑肌肌动力蛋白。(3)透射电镜观察21d组增厚的重塑血管壁,位于内外弹性膜之间的细胞为成肌纤维细胞表型,外层具有与它紧密联系的成纤维细胞。结论:成纤维细胞转化为成肌纤维细胞是低氧性肺血管重塑的重要原因之一。Objective To investigate the cell source for the muscularization of non-muscular pulmonary arterioles in hypoxia-induced pulmonary hypertension （HPH）. Methods Forty male Wistar rats were equally randomized to either a control group or groups with hypoxia for 3, 7, 14, and 21 days （groups H3, HT, Hi4, and H21）. The rat model of HPH was then constructed in the hypoxic groups. Mean pulmonary arterial pressure （mPAP） and right ventricular hypertrophy index （RVHI） were measured, and hypoxic pulmonary vascular remodeling （HPSR） was detected using morphometric analysis. Transformation of human embryonic lung fibroblast phenotypes was observed by cell culture. Uhrastructure of the microvessels in the rat lung was observed under transmission electron microscopy. Results （l）There were significant differences between group H7 and the control group in mPAP, the ratio of vascular wall area to total area （WA）, and the ratio of vascular lumen area to total area （LA） [（18.41 ±0.37） mmHg vs （14.02 ± 0.41） mmHg, （52.2 ± 0.8）% vs （64.5 ± 1.3）% and （47.8 ±0.8）% vs （35.5 ± 1.3）%, respectively; P 〈 0.05]. These parameters remained at a high level stably from day 14 of hypoxia. RVHI was markedly higher on day 14 of hypoxia than that in the control group [ （25.0 ± 1.8）% vs （23.6 ± 0.5）%, P 〈 0.05]. （2）Cell culture showed that α- SMA was partially expressed on human embryonic lung fibroblasts 72 hours after hypoxia. （3）The observation on the thickened remodeling vascular wall by electron microscopy 21 days after hypoxia revealed that the cells lining between the internal and external elastic lamina of the wall became myofibroblast phenotypes, which were closed connected with the fibroblasts in the external lamina. Conclusion The transformation of fibroblasts into myofibroblasts is one of the important causes in hypoxic pulmonary vascular remodeling.

关 键 词：高血压 肺性 成肌细胞 平滑肌 低氧血症 

分 类 号：R363[医药卫生—病理学]