Su Xiaoli, Peng Shurong, He Ruoxi, Hu Chengping, He Jun, Pan Pinhua
Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha 410008,China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2013 Jul;38(7):676-80. doi: 10.3969/j.issn.1672-7347.2013.07.004.
To examine the pathological change and intima thickness of thoracic aorta, detect the serum concentration of hypoxia-inducible factor-1α (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.
Twenty-four male Sprague-Dawley (SD) rats were divided into 4 groups: a CIH+Nacetylcysteine (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 of HIF-1α, ox-LDL, and PTX3 were detected by ELISA. The thickness of intima was taken by computer digital image analysis.
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 of intina (P<0.001).
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.
观察慢性间歇性缺氧（CIH）大鼠模型胸主动脉的病理变化及内膜厚度，检测血清中缺氧诱导因子-1α（HIF-1α）、氧化型低密度脂蛋白（ox-LDL）和五聚素3（PTX3）的浓度，以明确CIH对动脉内膜损伤的影响及其可能机制。
将24只雄性Sprague-Dawley（SD）大鼠分为4组：CIH+N-乙酰半胱氨酸（NAC）组、CIH+生理盐水（NS）组、CIH对照组和对照组。CIH组大鼠每180秒接受一次缺氧（氮气中6%-8%氧气，持续20-25秒）和常氧（氮气中21%氧气，持续2分钟）的交替循环，每天7小时。对照组大鼠不做处理。CIH+NAC组大鼠腹腔注射NAC[800 mL/（kg·d）]，CIH+NS组大鼠腹腔注射NS[5 mL/（kg·d）]。处理42天后，处死大鼠，取血并剪下胸主动脉。采用酶联免疫吸附测定法（ELISA）检测血清中HIF-1α、ox-LDL和PTX3的浓度。通过计算机数字图像分析测量内膜厚度。
CIH组和CIH+NS组大鼠胸主动脉出现血管内皮细胞损伤和脱落。CIH组和CIH+NS组的内膜比对照组和CIH+NAC组厚（P<0.001）。CIH组和CIH+NS组血清中HIF-1α、ox-LDL和PTX3的浓度高于对照组和CIH+NAC组（P<0.001）。血清中HIF-1α、ox-LDL和PTX3两两呈正相关，ox-LDL和PTX3的血清浓度与内膜厚度呈正相关（P<0.001）。
CIH可导致血管内皮细胞损伤和动脉内膜增厚。CIH激活氧化应激并升高HIF-1α、ox-LDL和PTX3水平是其重要机制。
