宫内慢性缺氧对子代大鼠中老年期血管内皮功能及一氧化氮合酶表达的影响

The role of intrauterine chronic hypoxia on vascular endothelial function and nitric oxide synthase expression in middle and old age rats offspring

背景不良宫内环境暴露增加日后发生成年心血管病的危险,缺氧是与临床最重要和最相关的产前应激,但目前有关宫内缺氧与日后中老年期血管内皮功能的关系尚不明确。目的探讨宫内慢性缺氧对子代大鼠中老年期血管内皮功能及一氧化氮合酶表达的影响。方法 SD孕鼠于妊娠第7天至第21天,采用低压氧舱,调节氧气浓度至(10±1)%,每日缺氧3h。采用离体胸主动脉环等长张力测定法检测16月龄子代大鼠血管内皮依赖性舒张功能改变(乙酰胆碱诱导的最大舒张百分比),并采用RT-PCR和Western blot技术检测血管组织诱导型一氧化氮合酶(i NOS)及内皮型一氧化氮合酶(eNOS)的表达情况。结果宫内缺氧组胸主动脉环内皮依赖性舒张功能低于正常对照组[(45.1±14.4)%比(82.7±10.6)%,t=5.14,P<0.01]。与正常对照组相比,宫内缺氧组i NOS mRNA与蛋白水平表达均明显上调,而eNOS mRNA与蛋白水平表达明显下调。结论慢性宫内缺氧可诱发子代大鼠中老年期内皮功能障碍,可能通过程序控制血管i NOS、eNOS异常表达而介导。

Background Exposure to an adverse intrauterine environment increases the risk of cardiovascular diseases later in the life.Hypoxia is one of the most important prenatal insult.However,the relationship between intrauterine hypoxia and the vascular endothelial functions in aged offspring remains unknown.Objective To study the effects of fetal chronic intrauterine hypoxia on the vascular endothelial functions and the expression of nitric oxide synthase later in the life.Methods Pregnant Sprague-Dawley rats were exposed to hypoxia for 3 hours/d in low pressure cabin with an oxygen concentration of（10±1）% from day 7 to 21 of pregnancy.For the offspring,at the age of 16 months,endothelial dependent dilatation function was evaluated by isometric tension of isolated rat thoracic aorta ring assay and the mRNA and protein expression of inducible nitric oxide synthase（iNOS）;endothelial nitric oxide synthase（eNOS）in the aorta were determined by RT-PCR and Western blot.Results There was a significant reduction in the endothelial dependent dilatation between intrauterine hypoxia group and the controls [（45.1±14.4）% vs（82.7±10.6）%,t=5.14,P0.01].The iNOS was significantly up-regulated and eNOS down-regulated in intrauterine hypoxia group both at mRNA and protein level compared to the controls.Conclusion Rats intrauterine chronic hypoxia impairs vascular endothelium functions in their aged offspring.These effects might be mediated by abnormal expressions of iNOS and eNOS in the blood vessels.