高肺血流量所致肺动脉高压大鼠肺血管结构和气体信使分子的变化

Alteration of pulmonary vascular structure and gaseous molecules in rats with pulmonary hypertension induced by high pulmonary blood flow

目的 :探讨高肺血流量所致肺动脉高压大鼠肺血管结构和两种气体信使分子的变化。方法 :对大鼠行腹主动脉 -下腔静脉分流术。 1 1周后 ,以右心导管法测定肺动脉平均压 (PAMP)。检测右心室 /体重 (RV/BW )和右心室 /左心室 +室间隔 (RV/LV +S)比值。观测肺血管显微及超微结构的变化。并且以分光光度计测定血浆一氧化氮 (NO)和一氧化碳 (CO)含量 ,以免疫组织化学方法检测肺动脉内皮细胞内皮型NO合酶 (eNOS)和平滑肌细胞血红素加氧酶 - 1 (HO - 1 )的表达。结果 :分流组大鼠PAMP、RV/BW及RV/ (LV +S)比值明显高于对照组 (P均<0 0 1 )。光镜下 ,肺小血管肌化程度明显增强 ,肺中、小型肌型动脉相对中膜面积及厚度明显增加。电镜下 ,肺腺泡内动脉内皮细胞增生、变性 ,内弹力层粗细不均 ,平滑肌细胞肥厚、向合成表型转化。并且分流组大鼠血浆NO含量明显高于对照组 (P <0 0 1 ) ,肺动脉内皮细胞eNOS表达明显增强。而分流组大鼠血浆CO含量和肺动脉平滑肌细胞HO - 1表达与对照组相比无明显变化。结论 :肺血管结构重建是左向右分流所致肺动脉高压的重要病理基础 。

AIM: To examine the alteration of pathologic structure and gaseous molecules in rats with pulmonary hypertension induced by high pulmonary blood flow.METHODS: Aortocaval shunting was produced for 11 weeks in rats, and pulmonary hemodynamics was evaluated.Pulmonary vascular micro- and ultra- structure was also examined.Meanwhile,the concentration of plasma nitric oxide (NO) and carbon monoxide (CO) was measured by spectrophotometry.The expression of endothelial nitric oxide synthase (eNOS) and heme oxygenase-1 (HO-1) in pulmonary arteries was detected by immunohistochemistry.RESULTS: After 11- week aortocaval shunting,pulmonary artery mean pressure was significantly increased.Muscularization of small pulmonary vessels and relative medial thickness and area of pulmonary arteries were obviously increased in shunting rats compared with controls.Ultrastructure of intrapulmonary arteries changed obviously in shunting rats.Meanwhile,plasma NO concentration was increased and eNOS expression in pulmonary artery endothelial cells was significantly augmented in rats of shunting group.Plasma carbon monoxide level and HO-1 expression in puomonary artery smooth muscle cells,however,were not altered in shunting rats.CONCLUSIONS: Pulmonary vascular structural remodeling is the important pathologic basis of pulmonary hypertension induced by a left-to-right shunt,and NO other than CO might play an important regulating role in the development of high pulmonary blood flow-induced pulmonary hypertension.