缺氧性肺动脉高压大鼠肺血管病变及其机制的实验研究

EXPERIMENTAL STUDY OF PATHOLOGICAL CHANGES IN PULMONARY VESSELS AND THEIR MECHANISMS UNDERLYING HYPOXIC PULMONARY HYPERTENSION IN RATS

模拟海拔 5km高原连续缺氧 ,制备缺氧性肺动脉高压 (HPH)大鼠动物模型 ,应用光镜、电镜、组织化学等方法 ,研究缺氧后 10、2 0、30天和对照组大鼠肺血管病理变化及其机制。发现缺氧后各时相各级肺小动脉管壁增厚、管腔狭窄 ,尤以 2 0天为著。主要表现为中膜平滑肌细胞 (SMC)增生 ,内弹力膜增厚 ,外膜胶原纤维增多。肺腺泡内无肌型和部分肌型动脉SMC增生、肌化 ,使肌型动脉数量增加 ;缺氧各组肌型动脉数量与对照组比较差异非常显著 (P <0 0 1)。缺氧后肺毛细血管基底膜不规则增厚 ;内皮细胞肿胀、胞质电子密度降低 ,饮泡增多 ,有的胞质形成乳头突向腔面 ;多数毛细血管充血、瘀血 ,中性粒细胞嵌塞 ,血小板聚集。表明缺氧可引起肺血管结构重塑 ,肺血流阻力增加 ,导致HPH。肺毛细血管超微结构病变所致的肺微循环障碍也是HPH发生。

A model of hypoxic pulmonary hypertension (HPH) was reproduced in rats by exposing them to chronic hypoxia environment corresponding to 5km level. At 10d,20d, 30d after hypoxia in hypoxia groups and control group, the pulmonary vascular structural changes were observed with optical microscope, histochemistry and electronic microscope. The changes in hypoxia groups were as follows: ①the wall of small pulmonary arteries of every calibre showed marked thickening compared with that in control group, and the main changes involved smooth muscle cells(SMC)proliferation and collagen deposition in the vessels wall; ② SMC proliferation, muscularization of non myocytic arteries and partial myocytic arteries were observed in intra acinar pulmonary arteries, so the counts of muscular arteries significantly increased compared with control group( P <0 01); ③ In the capillaries, swelling and degeneration of endothelial cells, thickening of base membranes, congestion, accumulation of polymorphonuclear neutrophils and platelets were found. Our findings suggested that chronic hypoxia could induce structural remodeling of small pulmonary arteries,leading to an increase in pulmonary arterial pressure. The disturbance of pulmonary micro circulation induced by the ultrastructural changes in pulmonary capillaries after hypoxia was an important cause of the production and development of HPH.