间断缺氧习服大鼠血浆、肺组织血管内皮生长因子变化及意义

目的 探讨间断缺氧习服对在鼠血浆、肺组织血管内皮生长因子（VEGF）含量的影响，为进一步认识高原水肿发病及高原习服机理提供实验依据。方法 40只雄性Wistar大鼠分为常氧对照组、急性缺氧组和3组间断缺氧习服组（IHa、b、c）。急性缺氧组直接在低压舱中模拟海拔8000m缺氧4h，间断缺氧习服组分别在低压舱中模拟不同海拔高度及不同时间进行间断缺氧习服，每天4h，间断缺氧习服后的大鼠再进行急性缺氧（低压舱中模拟8000m，4h）。用酶标记免疫吸附测定法测定大鼠血浆VEGF水平，免疫组化方法测定肺组织VEGF表达。结果 缺氧大鼠血浆及肺组织VEGF较对照组明显升高，差异有非常显著性意义（P＜0．01），以急性缺氧组升高明显（P＜0．01）；急性缺氧组肺组织有液体渗出及微血管内血球淤积现象；间断缺习服大鼠血浆及肺组织VEGF升高幅度较急性缺氧组明显降低，差异有显著性意义（P＜0．05），而且随间断缺氧习服时间的延长，升高幅度呈下降趋势，肺组织液体渗出明显好转。结论 极度缺氧导致VEGF显著升高可能是血管通透性增加的重要原因；VEGF与高原肺水肿的发病及高原习服密切相关。

The changes of vascular endothelial growth factor level in plasma and lung of rats during intermittent hypobaric hypoxia and its significance

Objective To investigate the mechanisms of high altitude pulmonary edema and high altitude acclimatization. Methods Forty Wistar rats were divided into five groups: normal control group, acute hypoxia group (exposed to a simulated 8 000 m altitude for 4 hours), and 3 intermittent hypoxia(4 h/d) groups [exposed to a simulated 3 000 m 4 h/d for 2 weeks(IHa) and 5 000 m altitude 4 h/d for 1(IHb) or 2(IHc) weeks, and then exposed to 8 000 m altitude for 4 h]. Plasma VEGF level was measured with ELISA method, and VEGF expression in lung was detected with immunohistochemistry method. Results Plasma and lung VEGF levels in rats exposed to hypoxia were significantly higher than those in NC group( P <0.01), and VEGF level in AH group was significantly higher than those in intermittent hypoxia groups( P <0.05). There was leakage of fluid in lung tissue of acute hypoxia group. The longer the rats underwent intermittent hypoxia exposure, the lower the VEGF level, and the less fluid leaked in lung tissue. Conclusions It is suggested that the increase of plasma and lung VEGF level during severe hypoxia may strongly enhance the vascular permeability, which may result in pulmonary edema. The change of VEGF level may play an important role in the mechanism of high altitude pulmonary edema and high altitude acclimatization.