低氧大鼠肺内酪氨酸激酶受体flk-1表达与肺血管重建

目的　评价酪氨酸激酶受体 flk- 1在低氧性肺血管重建中的变化和作用。方法　以常压间断低氧建立大鼠肺动脉高压模型 ,以微导管法测定大鼠肺动脉压 ,采用免疫组织化学染色法检测模型大鼠肺内 flk- 1的表达 ,对肺组织切片进行图象分析。结果　低氧 3周后 ,大鼠形成明显的肺动脉高压、肺小动脉壁细胞数增多 ,以及管壁增厚和管腔狭窄 ,表现为管壁厚度占外径的百分比 (WT% )和管壁面积占血管总面积的百分比 (WA% )明显升高 (P<0 .0 1) ;肺小动脉内膜的 flk- 1免疫阳性染色在低氧大鼠组明显增强 (P<0 .0 1) ,与 WT%和 WA%呈明显正相关 (r分别为 0 .714和 0 .738,P<0 .0 1)。结论　慢性低氧介导 flk- 1表达增多 ,可能在低氧性肺血管重建和肺动脉高压的发病过程中起一定的作用

The Expression of Tyrosine-kinase Receptor flk-1 and Hypoxic Pulmonary Vascular Remodeling in the Lung of Rats Exposed to Hypoxia

Objective To assess the role of tyrosine kinase receptor flk 1 in the development of hypoxic pulmonary vascular remodeling. Methods We divided 20 male Wistar rats into two groups(control vs hypoxia) and exposed them to normoxic condition and isobaric hypoxia for 3 weeks respectively. The pulmonary artery pressure was measured by right cardiac catheterization. The expression of flk 1 in lung tissues was measured by immunohistochemical staining. Histologic sections of the lungs were examined by a computerized image analyser. Results In hypoxic rats, the pulmonary artery pressure was significantly raised to a higher level, P< 0.01; the cell number of vascular wall was significantly increased. The results also demonstrated that chronic hypoxia brought about the significant increment in thickness of wall with narrowing of lumen of pulmonary arterioles, and the increment in the percent of vascular wall thickness/vascular external diameter (WT%) and the percent of vascular wall area/total vacular area (WA%), P< 0.01. The positive staining of flk 1 in the wall of pulmonary arteriole of rats treated with hypoxia was significantly stronger than that of normal rats, P< 0.01. Positive correlations were seen between the increment of expression of flk 1 with WT% and WA% ( r =0.714, 0.738, P< 0.01). Conclusion Chronic hypoxia can induce an increasing expression of flk 1, and the flk 1 may play an important role in the pathogenesis of hypoxic pulmonary vascular remodeling.