慢性间断低氧模型大鼠动脉内膜损伤及相关途径分析  

Endarterium injury and the related pathway in chronic intermittent hypoxia rats

作　　者：苏晓丽[1] 彭殊蓉 贺若曦[1] 胡成平[1] 何俊[1] 潘频华[1] 

机构地区：[1]中南大学湘雅医院呼吸内科,长沙410008 [2]湖南省岳阳市一人民医院综合内科,湖南岳阳414000

出　　处：《中南大学学报（医学版）》2013年第7期676-680,共5页Journal of Central South University ：Medical Science

基　　金：湖南省科技厅科技计划项目(2010SK3106)~~

摘　　要：目的:通过对慢性间断低氧(CIH)大鼠动脉内膜病理改变及厚度的观察和血管炎症因子变化的检测,探讨CIH对动脉内膜的损伤及其可能的途径。方法:24只成年Sprague-Dawley雄性大鼠随机分为4组:慢性间断低氧组(CIH组),慢性间断低氧+N-乙酰半胱氨酸干预组(CIH+NAC组)、慢性间断低氧+生理盐水组(CIH+NS组)和常氧对照组(control组),每组6只。经相应处理42 d后处死大鼠取心脏血和胸主动脉。ELISA法检测低氧诱导因子-1α(HIF-1α),氧化低密度脂蛋白(ox-LDL),正五聚蛋白3(PTX3)血清浓度,观察胸主动脉病理变化,通过计算机图像分析系统测定动脉内膜厚度。结果:CIH组及CIH+NS组大鼠胸主动脉内皮细胞部分受损脱落,少量单核细胞、巨噬细胞浸润,动脉内膜厚度与对照组比较均明显增厚(P<0.001);CIH+NAC组大鼠胸主动脉内膜厚度与CIH组及CIH+NS组比较显著减小(P<0.001)。CIH组及CIH+NS组大鼠血清HIF-1α,ox-LDL,PTX3浓度与对照组比较明显增高(P<0.001)。CIH+NAC组大鼠血清HIF-1α,ox-LDL,PTX3水平较CIH组及CIH+NS组明显降低(P<0.001)。大鼠血清HIF-1α,ox-LDL,PTX3浓度间呈正相关,ox-LDL,PTX3浓度与胸主动脉内膜厚度呈正相关(P<0.001)。结论:CIH可损伤血管内皮细胞,使动脉内膜增厚。CIH通过激活氧化应激状态,增加HIF-1α,ox-LDL,PTX3等因子的产生是导致血管内皮损伤的一个重要途径。Objective： To examine the pathological change and intima thickness of thoracic aorta, detect the serum concentration of hypoxia-inducible factor-1 α （HIF-1α）, oxidized LDL （ox-LDL）, and pentraxin 3 （PTX3） in the rat model of chronic intermittent hypoxia （CIH）, and to determine the effect of CIH on endarterium injury and its possible pathway.Methods： Twenty-four male Sprague-Dawley （SD） rats were divided into 4 groups： a CIH＋N- acetylcysteine （NAC） group, a CIH＋normal saline （NS） group, a CIH control group and a control group. CIH rats were subjected to alternating cycles of hypoxia （6%-8% O2 in N2 for 20-25 s） and normoxia （21% O2 in N2 for 2 min） every 180 s for 7 h/d. Rats in the control group were not treated. Rats in the CIH＋NAC group were treated with NAC [800 mL/（kg.d）] intraperitoneal injection, and rats in the CIH＋NS group were treated with NS [5 mL/（kg.d）] intraperitoneal injection. After 42 day treatment, the rats were sacrificed, blood taken, and thoracic aorta cut off. The serum concentration ofHIF-1α, ox-LDL, and PTX3 were detected by ELISA. T-he thickness of intima was taken by computer digital image analysis. Results： Vascular endothelial cell injury and detachment were found in the thoracic aorta in the CIH and the CIH＋NS group. The intima in the CIH and the CIH＋NS group was thicker than that in the control and the CIH＋NAC group （P〈0.001）. The serum concentration of HIF-1α, ox-LDL, and PTX3 in the CIH and the CIH＋NS group was higher than that in the control and the CIH＋NAC group （P〈0.001）. The serum concentration of HIF-1α, ox-LDL, and PTX3 was pairwise positive correlation, and the serum concentration of ox-LDL and PTX3 was positively correlated with the thickness ofintina （P〈0.001）. Conclusion： The vascular endothelial cell injury and endarterium thickening can be induced by CIH. It is an important pathway that CIH activates oxidative stress and elevates the levels of HIF- 1α, ox-LDL, and PTX3.

关 键 词：阻塞性睡眠呼吸暂停 慢性间断性低氧 低氧诱导因子-1Α 氧化低密度脂蛋白 正五聚蛋白3 动 脉内膜厚度 N-乙酰半胱氨酸 

分 类 号：R56[医药卫生—呼吸系统]