血管内皮细胞生长因子与高原肺水肿发病的关系

Research on the relationship between expression of VEGF and high altitude pulmonary edema

目的 探讨血管内皮细胞生长因子 (VEGF)表达变化在高原肺水肿发病、高原习服 适应中的意义。方法 培养大鼠肺动脉血管内皮细胞 ,采用RT -PCR方法和酶联免疫吸附 (ELISA)方法分别观察低氧 (体积分数为 1%的O2 )时细胞及培养液中VEGF表达变化 ;将大鼠分为 5组 ,分别模拟不同海拔高度、不同时间进行间断低氧习服 ,每天 4h ,间断低氧习服后的大鼠再进行急性低氧(80 0 0m ,4h)。用免疫组织化学及RNA狭缝杂交方法测定急性低氧和低氧习服不同时间、不同海拔高度大鼠肺组织VEGF变化 ,并对肺组织切片进行初步病理分析 ;采用ELISA方法测定大鼠、高原移居者及高原肺水肿患者治疗前后血浆中VEGF水平。结果 低氧时大鼠肺动脉血管内皮细胞VEGF表达水平明显升高 (P <0 .0 1) ;低氧大鼠 (包括急性低氧组及间断低氧习服组 )血浆及肺组织VEGF较常氧对照组明显升高 (P <0 .0 1) ;急性低氧组大鼠肺组织有液体渗出 ;间断低氧习服大鼠血浆及肺组织VEGF较急性低氧组升高幅度明显降低 ,而且随间断低氧习服时间的延长 ,升高幅度呈下降趋势 ,肺组织液体渗出逐渐消失 ;移居高原的汉族居民血浆中VEGF水平明显高于藏族居民 (P <0 .0 1) ;移居高原 1周的汉族居民血浆中VEGF水平明显高于移居 6个月的汉族居民 ;

Objective To investigate the relationship between the expression of VEGF and the incidence of high altitude pulmonary edema (HAPE) and the mechanism of high altitude acclimatization-adaptation. Methods Pulmonary artery endothelial cells (PAEC) of rat were cultured. The expression of VEGF in PAEC was detected using RT-PCR and ELISA. Rats were divided randomly into five groups by weight: control, acute hypoxia (exposed to a simulated 8 000 m altitude for 4 hours), and three intermittent hypoxia groups (exposed to a simulated 3 000 m or 5 000 m altitude for 2 weeks, 4 hours a day, then to a simulated 8 000 m altitude for 4 hours). VEGF in the lung was detected using immunohis to chemistry and slot hybridization, and the changes of pathology in the lung were observed. VEGF in the blood plasma of rats, in men who immigrated to high altitude at different times, and in those who suffered from high altitude pulmonary edema were measured using ELISA. Results The expression of VEGF in PAEC was increased under hypoxia condition (1% O 2) ( P <0.01). In the blood plasma and lung of rats during hypoxia, levels of VEGF and VEGF mRNA were higher than that in the control group. VEGF in acute hypoxia group was increased significantly compared with that in the intermittent hypoxia groups. Leakage of fluid in the lung of rats was observed in the acute hypoxia group. The longer the rats acclimatized, the lower the level of VEGF expressed, and the less the fluid leaked in the lung. The same tendency could be seen in humans. The level of VEGF in patients with high altitude pulmonary edema pre-therapy was higher than that measured post-therapy. Conclusions Hypoxia could stimulate the expression of VEGF, and the upregulated expression of VEGF is one of the most important factors of incidence of high altitude pulmonary edema.