慢性间歇性低压低氧通过磷脂酰肌醇3激酶依赖的内皮型一氧化氮合酶活化增强大鼠肾动脉舒张  

Chronic intermittent hypobaric hypoxia enhances the vasodilatation of renal artery via phosphoinositide 3-kinase-dependent endothelial nitric oxide synthase activation in rats

作　　者：王立轩[1] 许新[2] 张璐[2] 刘敏[3] 王亚萍[3] 马慧娟[3,4] 

机构地区：[1]河北医科大学组织胚胎学教研室,河北石家庄050017 [2]河北医科大学,河北石家庄050017 [3]河北医科大学生理学教研室,河北石家庄050017 [4]河北医科大学河北省实验动物重点实验室,河北石家庄050017

出　　处：《中华高血压杂志》2016年第8期735-740,共6页Chinese Journal of Hypertension

基　　金：国家自然科学基金(31100832);河北省自然科学基金(C2013206183,C2013206174);国家级大学生创新实验资助项目(201310089004)

摘　　要：目的探讨慢性间歇性低压低氧(CIHH)处理对大鼠离体肾动脉环舒张活动的影响及其机制。方法成年雄性SD大鼠48只,随机分为对照组(n=24)和CIHH组(n=24)。CIHH组大鼠给予模拟海拔5000m高度的低压低氧处理(大气压404mm Hg,氧分压84mm Hg),6h/d,持续28d。对照组动物同期饲养,不接受低氧处理。通过离体血管环灌流记录肾动脉的舒张活动。Western bolt法检测肾动脉组织中内皮型一氧化氮合酶(eNOS)和磷脂酰肌醇3激酶(PI3K)的蛋白表达水平。结果与对照组相比,CIHH处理可以增强乙酰胆碱引起的肾动脉舒张[CIHH组比对照组:乙酰胆碱10^(-7.5) mol/L时为(23.52±3.57)%比(13.45±2.46)%(n=8),P<0.05;乙酰胆碱10^(-5) mol/L时为(78.72±6.13)%比(49.53±6.64)%(n=8),均P<0.05];CIHH可以提高肾动脉组织中eNOS的表达,并提高肾动脉组织中一氧化氮水平[(675.29±56.67)比(397.17±43.66)μmol/g(n=10),P<0.05]。CIHH处理可提高肾动脉组织中PI3K的表达(P<0.05)。PI3K阻断剂LY294002可以阻断CIHH对肾动脉舒张及eNOS表达的增强作用(P<0.05)。结论 CIHH处理可能通过PI3K途径活化eNOS,增强乙酰胆碱诱导的大鼠肾动脉舒张。Objective To investigate the effects of chronic intermittent hypobaric hypoxia （CIHH） on the vasodilatation of isolated renal artery and the underlying mechanism in rats. Methods Forty-eight adult male Sprague- Dawley rats were randomly divided into two groups： control group（n=24） and CIHH group（n=24）. The rats in the CIHH group were exposed to hypobaric hypoxia simulating 5000 m high altitude （barometric pressure： 404 mm Hg, oxygen partial pressure： 84 mm Hg） for 28 days, with 6 hours each day. The rats in the control group were raised in the normoxic environment in the corresponding period. The vasodilatation of renal artery was recorded by isolated vessel ring perfusion method. The protein expression levels of endothelial nitric oxide synthase （eNOS） and phosphoinositide 3 kinase （PI3K） in renal artery tissues were determined by Western blot. Results Compared to the control group, the treatment with CIHH could remarkably enhance acetylcholine （ACh）-induced vasodilatation of renal artery[Ach（10^-7.5 mol/L）： （23.52±3.57）% vs （13.45±2.46）% （n：8）, P〈0.05;Ach（10^-5 mol/L）： （78.72±6.13）% vs （49.53±6.64）% （n=8）, P〈0.05]; and the treatment with CIHH could increase the expression of eNOS and the concentration of nitric oxide [（675.29±56.67） vs （397.17±43.66）μmol/g （n=10）, P〈0. 05] in the renal artery tissues. The treatment with CIHH could improve the expression of PI3K in the renal artery tissues （P〈0.05）. PI3K inhibitor LY294002 could block the vasodilatation of renal artery and the increase in the expression of eNOS caused by CIHH （P〈0.05）. Conclusion The treatment with CIHH enhances ACh-induced vasodilatation of renal artery possibly by activating eNOS via PI3K pathway.

关 键 词：慢性间歇性低压低氧 肾动脉舒张 内皮型一氧化氮合酶 磷脂酰肌醇3激酶 

分 类 号：R544.1[医药卫生—心血管疾病]