低氧对大鼠不同节段肺动脉一氧化氮合酶mRNA表达的影响

Hypoxia impacts expression of nitric oxide synthase mRNA of different segments of intrapulmonary arteries

目的探讨正常状态下肺动脉结构型一氧化氮合酶（ｃＮＯＳ）基因表达的定位及慢性低氧对不同节段肺动脉ｃＮＯＳ基因表达的影响。方法应用原位杂交技术，采用ｃＮＯＳｃＲＮＡ探针，观察低氧１周组、低氧２周组及对照组大鼠肺动脉ｃＮＯＳｍＲＮＡ的表达与分布。结果对照组大鼠与细支气管伴行的肺动脉内皮细胞ｃＮＯＳｍＲＮＡ的表达明显高于与呼吸细支气管及终末细支气管伴行的肺动脉（ｑ＝８１３，５４９；Ｐ均＜００１）。低氧１周及２周组大鼠与终末细支气管及细支气管伴行之肺动脉内皮细胞ｃＮＯＳｍＲＮＡ表达较对照组大鼠均明显降低。对照组大鼠各级肺动脉平滑肌细胞ｃＮＯＳｍＲＮＡ表达差异无显著意义（Ｆ＝２２６，Ｐ＞００５）；低氧１周及２周组大鼠与呼吸细支气管及终末细支气管伴行之肺动脉平滑肌细胞ｃＮＯＳｍＲＮＡ表达较对照组大鼠均明显降低。结论正常大鼠近端肺动脉内皮细胞ｃＮＯＳｍＲＮＡ表达强度最高；慢性缺氧主要抑制近端肺动脉内皮细胞及远端肺动脉平滑肌细胞ｃＮＯＳｍＲＮＡ的表达。

Objective To investigate expression and localization of nitric oxide synthase (cNOS) mRNA of normoxic pulmonary arteries and the impact of hypoxia on its expression. Methods In situ hybridization was performed on each lung sections from rats in 1 week hypoxic group, 2 week hypoxic group, and control group to detect cNOS mRNA expression and localization by using cRNA probe for NOS. Results The positive score of cNOS mRNA expression by endothelial cells of pulmonary arteries associated with bronchioli was significantly higher than that of arteries associated with respiratory or terminal bronchioli ( q =8.13, 5.49, P <0.01) in the control rats. In the 1 week hypoxic group or the 2 week hypoxic group, however, cNOS mRNA expression by endothelial cells of pulmonary arteries associated with either respiratory or terminal bronchioli was markedly decreased compared with that of the control group. No significant difference was found in cNOS mRNA expression by smooth muscle cells of each segments of pulmonary arteries ( F =2.26, P >0.05). However, cNOS mRNA expression by smooth muscle cells of pulmonary arteries associated with respiratory bronchioli or terminal bronchioli was significantly decreased in the 1 week or the 2 week hypoxic group compared with the control group. Conclusion These findings suggest that NOS mRNA expression by endothelial cells is greater in the larger, more proximal pulmonary arteries than at the periphery. Chronic hypoxia mainly impairs cNOS mRNA expression by proximal pulmonary artery endothelial cells and periphery pulmonary artery smooth muscle cells.