慢性间歇性低压低氧通过PI3K依赖的eNOS活化增强大鼠胸主动脉舒张

Chronic intermittent hypobaric hypoxia enhances the vasodilatation of thoracic aorta via PI3K-dependent eNOS activation in rats

目的探讨慢性间歇性低压低氧(CIHH)对大鼠胸主动脉环舒张活动的影响及其一氧化氮相关机制。方法成年雄性SD大鼠80只,随机分为对照组(CN组)和慢性间歇性低压低氧组(CIHH组),每组40只。CIHH组给予模拟海拔5 000 m(PB=404 mm Hg,PO2=84 mm Hg)的低压低氧处理,6 h/d,共28 d。对照组处于常压常氧环境,平行饲养。应用离体血管环灌流记录胸主动脉的舒缩活动;采用Western blotting法检测胸主动脉组织中eNOS和PI3K的表达水平。结果与CN组相比,CIHH组乙酰胆碱引起的胸主动脉舒张明显增强(P<0.05),胸主动脉组织中eNOS的表达增多(P<0.05);M EK阻断剂PD98059孵育,对CN组和CIHH组无影响;PI3K阻断剂LY294002孵育,可阻断CIHH组胸主动脉舒张增强和eNOS表达增多(P<0.05);且CIHH组胸主动脉组织中PI3K的表达升高(P<0.05)。结论 CIHH处理可通过PI3K途径活化血管内皮eNOS,增强乙酰胆碱诱导的大鼠胸主动脉舒张。

Objective To investigate the effects of chronic intermittent hypobaric hypoxia（ CIHH） on the vasodilatation in isolated thoracic aorta and the nitric oxide related mechanism in rats. Methods A total of 80 male adult Sprague-Dawley rats were randomly divided into two groups： control group（ CN,n = 40） and CIHH group（ CIHH,n =40）. The rats in CIHH group were exposed to hypoxia simulating at 5000-meter altitude in a hypobaric chamber（ PB=404 mm Hg,PO2= 84 mm Hg） for 28 days,6 hours each day. The rats in CN group lived in a normoxic environment for the same period. The vasodilatation of thoracic aorta was recorded by using organ bath technique. The protein expressions of e NOS and PI3 K were measured by using Western blotting. Results CIHH could remarkably augment the acetylcholine（ ACh）-induced vasodilatation of thoracic aorta（ P〈0. 05） and increase the expression of e NOS in thoracic aorta tissues（ P〈0. 05）. Incubation with MEK inhibitor PD98059 did not affect the effects of CIHH on thoracic aorta.Incubation of PI3 K inhibitor LY294002 blocked the effects of CIHH（ P〈0. 05）. Furthermore,CIHH treatment could improve the expression of PI3 K in thoracic aorta tissue（ P〈0. 05）. Conclusion CIHH treatment enhances Ach-induced vasodilatation of thoracic aorta by activating e NOS via PI3 K pathway.