慢性间歇性低压低氧对大鼠离体肺动脉环舒张功能的影响*
Effects of chronic intermittent hypobaric hypoxia on pulmonary vasodilatation of rats

目的:探讨慢性间歇性低压低氧(CIHH)对大鼠离体肺动脉环舒张功能的影响及其机制。方法:成年雄性SD大鼠随机分为对照组、CIHH组、对照+阻断剂组和CIHH+阻断剂组。CIHH大鼠给予每天6 h模拟海拔5 000 m的低压低氧处理,对照置于常压常氧环境同期饲养,28 d后处死大鼠,制备肺动脉环,加阻断剂组给予终浓度为10 μmol/L MEK特异性阻断剂PD98059或PI3K阻断剂LY294002处理20 min。采用灌流实验记录乙酰胆碱诱导的肺动脉的舒张活动; 应用Western blot法检测肺动脉组织中eNOS的表达水平。结果:CIHH处理可增强乙酰胆碱引起的肺动脉舒张,提高肺动脉组织中eNOS的表达(P＜0.05); PD98059共孵育对CIHH的作用无影响(P＞0.05),LY294002共孵育可部分阻断CIHH的作用(P＜0.05)。结论:CIHH处理可能通过PI3K途径活化血管内皮eNOS,增强乙酰胆碱诱导的大鼠肺动脉舒张。
Aim: To investigate the effects of chronic intermittent hypobaric hypoxia(CIHH)on the vasodilatation of isolated pulmonary artery in rats and the underlying mechanism.Methods: Adult male SD rats were randomly allocated into 4 groups: control group, CIHH group, control+blocking agent group and CIHH+blocking agent group.The rats in CIHH groups were exposed to hypoxia simulating 5000 m high altitude in a hypobaric chamber for 28 d, 6 h each day. The rats in control group were maintained in a normoxic environment for a corresponding period. The rats in groups treated with blocking agent were given 10 μmol/L MEK inhibitor PD98059 or PI3K inhibitor LY294002 for 20 min.The vasodilatation of pulmonary artery was recorded by using organ bath technique. The protein expression level of eNOS in pulmonary artery tissue was measured by Western blot.Results: CIHH could remarkably augment the acetylcholine(ACh)induced vasodilatation of pulmonary artery and increase the expression of eNOS in pulmonary artery tissue(P＜0.05). Incubated with PD98059 did not affect the effects of CIHH on pulmonary artery. Incubation of LY294002 blocked the effects of CIHH(P＜0.05).Conclusion: The data demonstrate that CIHH treatment may enhance ACh induced vasodilatation of pulmonary artery by activating eNOS via PI3K pathway