产前缺氧程序控制6周龄兔颈动脉内皮依赖性舒张功能及其相关分子机制

Effects of Perinatal Hypoxia on Carotid Artery Endothelium-dependent Relaxations of 6 Weeks Old Rabbits and Its Molecular Mechanism

目的研究产前缺氧对6周龄新西兰兔颈动脉内皮依赖性舒张功能的影响及相关分子机制。方法同期怀孕的新西兰母兔随机分为常氧对照组(n=5)和缺氧组(12%O2,n=5),于妊娠第10天开始相应的干预,至妊娠第29天结束,自然分娩。每窝随机留1只雄性新生兔饲养,共得10只雄性新生兔,母乳喂养至6周。检测6周龄兔离体颈动脉内皮依赖性舒张功能;利用同位素方法测定内皮型一氧化氮合酶活性;利用Western blot、免疫组织化学法检测颈动脉内皮型一氧化氮合酶、热休克蛋白90表达。结果产前缺氧损伤6周龄兔颈动脉内皮依赖性舒张功能,降低内皮型一氧化氮合酶活性,下调热休克蛋白90表达(P<0.05)。结论产前缺氧通过下调6周龄兔颈动脉热休克蛋白90表达,降低内皮型一氧化氮合酶活性,从而损伤颈动脉内皮依赖性舒张功能。

Aim To investigate the effects of perinatal hypoxia on carotid artery endothelium-dependent relaxa- tions of 6 week old rabbits and its molecular mechanism. Methods Ten pregnant New Zealand White rabbits were randomly divided into two groups： normoxic control group （21% 02 , n = 5 ） and perinatal hypoxia group （ 12% O2, n = 5 ） during day 10 ~ 29 of pregnancy. Pregnant rabbits had spontaneous deliveries, and only one male offspring from each lit- ter was selected randomly and breast-fed for six weeks. Carotid arteries were obtained from 6 week old rabbits, endotheli- um-dependent relaxation （EDR） and expression of endothelial nitric oxide synthase （eNOS） and heat shock protein 90 （HSP90） of carotid arteries were examined. Results Perinatal hypoxia significantly impaired carotid artery EDR in 6 week old rabbits （ P 〈 0. 05 ）. Perinatal hypoxia significantly decreased carotid artery HSP90 expression （ P 〈 0. 05 ） and eNOS activities （ P 〈 0. 05 ） in 6 week old rabbits. Conclusions Perinatal hypoxia can induce functional impairment in vascular endothelium from 6 week old rabbits. The molecular mechanism involved is that perinatal hypoxia decrease HSP90 expression and eNOS activities of rabbit artery.