摘要
模拟海拔5000m连续低压缺氧7天复制大鼠肺动脉高压模型,观察结构重建的肺外动脉胶原含量及其基因表达的变化。结果表明:缺氧7天末,大鼠肺动脉压(PAP)、右心室/左心室十室间隔重量比值[RV/(LV+S)]及肺外动脉湿干重量和羟脯氨酸含量均明显升高;经Northern杂交和斑点杂交分析无交叉和非特异性杂交的编码人Proα_1(I)、Proα_1(III)肽链的cDNA探针,进行DNA-RNA的斑点杂交显示,缺氧组的Proα_1(I)、Proα_1(III)mRNA表达水平均明显升高、分别比对照组高1.5和1.8倍(P<0.05)。HE染色检查可见肺外动脉中、外膜均明显增厚,以外膜增厚最显著,约为对照组的2倍。透射电镜显示肺动脉主干中膜平滑肌细胞肥大,胞浆肌丝减少,突出增多,细胞向分泌型转化;外膜成纤维细胞增生肥大,分泌活跃;平滑肌细胞和成纤维细胞周围胶原纤维增多,以成纤维细胞周围胶原纤维增多明显。提示:慢性缺氧性肺动脉高压早期结构重建的肺外动脉外膜成纤维细胞的变化较中膜平滑肌细胞更明显;结构重建的肺外动脉胶原的堆积与胶原基因转录水平表达升高有关。
he change of collagen content and procollagen α_1(I) , α_1(III) mRNA expression in rat vascular struc-tural remodeling of extrapulmonary artery (EPA)in-duced by hypoxia were investigated.72 wistar malerats weighing 200~300g were used and divided into 2groups:air-breathing group(N group, 39 rats)andhypoxic group(Hgroup, 33 rats exposed to 5000m hy-pobaric hypoxia for 7 days ).ResuIts showed thatmPAp, Rv/(Lv + s ),the wet, dry weights and hy-poxyproline (HP) content in EPA of H group were in-creased from 2.83±0.09kPa(,0.23±0.01,5. 2±0.2mg,1.7±0.1mg and 22.3±1.0μg/100g BW(body weight) to 4. 77±0. 12kPa,0. 43±0.01,10.5±0.5mg,4.1±0. 2mg and 58.4±3.4μg/100g BW(body weight) to 4.77±0. 12kPa,0.43±0. 02,10.5±0. 5mg,4.1±0.2mg and 58.4±3.4μg/100g(all P<0.01). Dot Blot and Northern Blot hvbridization anal-yses showed that in EPA of H group procollagen α_1 (I)and α_1 (III)mRNAs were increased 154%and 177%(all P<0. 05).Histological study(HE)showed thathypoxia could induce an increase in the wall thicknessof EPA,particularly in adventitial thickness of the pul-monary arterial trunk.Electron microscopy revealedthe hypertrophied medial smooth muscle cells contain-ing a significant increase in rough endoplasmic reticu-lum(RER ),in extracellular ground,collagen fibersand elastin were increased.In adventitia,the fibrob-lasts showed both hypertrophy and hyperplasia andsorrounding collagen fibers were increased.Thesestudies suggested that fibroblast might play importantrole in the remodeling of EPA during the early hypoxicpulmonary hypertension and the increase of collagengene expression might be involved in the mechanism ofcollagen content and remodeling of EPA induced by hypoxia.
出处
《中华结核和呼吸杂志》
CAS
CSCD
北大核心
1994年第3期152-155,T017,共5页
Chinese Journal of Tuberculosis and Respiratory Diseases
关键词
胶原
成纤维细胞
肺性高血压
Hypoxic Pulmonary hypertensionCollagen Fibroblast