内源性一氧化碳对缺氧性肺动脉高压与肺血管结构调节的研究

Regulatory effect of endogenous carbon monoxide on hypoxic pulmonary hypertension and pulmonary vascular structure

目的 研究内源性一氧化碳 (CO)对缺氧性肺动脉高压 (PH)和肺血管结构的调节作用。方法 将18只Wistar大鼠随机分为对照组、低氧组、低氧 +ZnPP组。均以右心导管法测定肺动脉压力 ;对肺组织进行弹力纤维染色 ,测定肌型动脉百分比 ,以及肺中、小动脉的相对中膜面积 (RMA)、厚度 (RMT) ;采用免疫组织化学法检测Ⅰ、Ⅲ型胶原蛋白的表达 ,核酸原位杂交法检测肺动脉Ⅲ型前胶原 [Pro α1(Ⅲ )胶原 ]mRNA表达。结果 低氧组大鼠肺动脉压力明显高于对照组 ;低氧 +ZnPP组大鼠肺动脉压力明显高于低氧组 (P <0 .0 1)。低氧大鼠肌型动脉百分比和肺中、小肌型动脉RMA及RMT均明显增高 ;ZnPP促使低氧大鼠上述肺血管结构重建指标增高更加显著 (P均 <0 .0 1)。低氧大鼠肺动脉Ⅰ、Ⅲ型胶原蛋白及Pro α1(Ⅲ )胶原mRNA表达均显著增高 ,ZnPP促使低氧大鼠肺动脉Ⅰ、Ⅲ型胶原蛋白及Pro α1(Ⅲ )胶原mRNA表达更加明显 (P均 <0 .0 1)。结论 内源性CO在缺氧性PH和肺血管结构重建形成中发挥着重要的保护作用 。

Objective To explore the role of endogenous carbon monoxide (CO) in regulating hypoxic pulmonary hypertension and pulmonary vascular structure. Methods Eighteen Wistar rats were randomly divided into control group, hypoxic group and hypoxic with ZnPP group. Pulmonary artery mean pressure of each rat was evaluated using right cardiac catheterization. Lung tissues were dyed with Weighert′s method. The percentage of each type of intra-acinar pulmonary arteries was measured. Relative media thickness (RMT) and relative media area(RMA) of the intrapulmonary arteries were observed. Collagen Ⅰand collagen Ⅲ expressions were detected by immunohistochemical assay. The expressions of type Ⅲ procollagen [Pro-α 1(Ⅲ) collagen] mRNA were detected by situ hybridization. Results mPAP was significantly increased in hypoxic group as compared with that of controls;and mPAP in hypoxic with ZnPP group was markedly increased compared with that of hypoxic group (P<0.01).Percentage of muscularized artery,RMA and RMT of intra-pulmonary arteries were significantly increased in hypoxic group;ZnPP augmented mPAP and RMT and RMA markedly in hypoxic rats (P<0.01). In hypoxic rats the expressions of collagen Ⅰ,collagen Ⅲ proteins and Pro-α 1 (Ⅲ) collagen mRNA in pulmonary arteries were increased significantly compared with rats of control group. ZnPP elevated expressions of collagen Ⅰ,collagen Ⅲ proteins and Pro-α 1 (Ⅲ) collagen mRNA obviously(P<0.01). Conclusion Endogenous CO may act as a protective factor in hypoxic pulmonary hypertension and pulmonary vascular structure remodeling at least, which has partly involved in the regulation of CO in synthesis of collagen in pulmonary artery of hypoxic rats.