慢性间歇低氧老龄大鼠脑血管内皮功能的研究

目的 探讨慢性间歇低氧(CIH)对老龄鼠脑血管及内皮素-1(ET-1)、一氧化氮(NO)、血管内皮生长因子(VEGF)表达的影响.方法 应用间歇低氧处理方式建立CIH老龄大鼠实验模型,实验3、6、9周后,检测血浆ET-1、NO和VEGF的含量;观察脑血管病理变化与脑组织中小动脉血管壁厚度与外径之比(WT%)与VEGF蛋白的表达.结果 CIH组血ET-1、VEGF表达均增加,NO表达减弱,从第3周ET-1含量较空白对照(UC)组增高(t=2.47,P<0.05),VEGF含量较空白对照(UC)组升高(t=2.38,P<0.05),NO含量较UC组降低(t=2.39,P<0.05).VEGF水平与间歇低氧时间呈正相关,第9周[(171.1±13.5)pg/ml]表达最强,与第3周[(129.3±12.3)pg/ml]比较升高明显(t=2.38,P<0.05),较UC组[(109.8±8.6)pg/ml]增高(t=3.46,P<0.01).光镜下UC组脑血管未见明显的病理变化,CIH组可见脑细胞水肿和血管增生.CIH组大鼠脑小动脉WT%改变从第3周即强于UC组(t=2.34,P<0.05),脑组织VEGF的表达在CIH组各时间段均显著高于UC组(t=2.37,P<0.05),随着CIH作用时间的累积,脑组织VEGF和脑小动脉WT%改变均有加重的趋势,第9周明显高于第3周(t=2.32和t=2.35,均P<0.05).结论 CIH可诱导老龄大鼠ET-1、VEGF表达增强,NO水平下降,导致脑细胞肿胀,小动脉管壁增厚,管腔狭窄,提示纠正VEGF、ET-1/NO的表达紊乱应成为OSAS综合防治的一个重要方面.

Study on endothelial function of cerebral vessels in aged rats with chronic intermittent hypoxia

Objective To investigate the expression of endothelin-1 (ET-1 ), nitrogen monoxidium (NO), vascular endothelial growth factor (VEGF) and brain tissue VEGF induced by chronic intermittent hypoxia (CIH) in aged rats. Methods The CIH model of aged rat was established by using intermittent hypoxia. The levels of ET-1, NO and VEGF in the plasma were detected at 3, 6 and 9 weeks after experiment in each group. The expression of VEGF in brain tissues and the pathological changes of the vessels of the cerebra and the ratio between the thickness of vessel wall and external diameter (WT%) were observed. Results In CIH group, the ET-1 and VEGF levels increased, however NO level decreased. The levels of ET-1 and VEGF were higher at 3 weeks in CIH group than in UC group (t=2.47 and 2.38, both P<0.05), however NO level was lower in CIH group than in UC group (t=2.39, P<0.05). VEGF levels increased significantly at 9 weeks in CIH as compared with UC group [(171.1±13.5) pg/ml vs. (109.8±8.6) pg/ml, t = 3.46, P< 0.01]. The levels of VEGF in CIH group increased remarkably at 9 weeks as compared with 3 weeks [(129.3±12.3) pg/ml, t=2.38, P<0.053. VEGF levels in CIH group showed positive correlation with the time of intermittent hypoxia. The changes of cerebral vessels in UC group were not found, while the aged rats in CIH group showed cerebral neuron cells swelling and blood vessel hyperplasia. The WT% of cerebral small artery was more apparent in CIH group than in UC group at 3 weeks (t=2.34,P<0.05). The expression of VEGF in cerebra was higher in CIH group than in UC group in the three stages (r=2.37, P<0.05). There was an aggravated tendency in the change of the expression of brain tissue VEGF and WT% over time. The change was more apparent at 9 weeks than at 3 weeks (t=2.32 and 2.35, both P<0.05). Conclusions CIH can induce an increase in the expression of ET-1 and VEGF, a decrease in the expression of NO in aged rats. The over expression of VEGF and the disbalance of ET-1 and NO levels can cause brain cellular swelling, arteriola vessel wall thickening,lumens stenosis.