慢性间歇低氧对大鼠肝CXC趋化因子配体10表达的影响及抗氧化剂的干预作用

目的：通过大鼠模型观察慢性间歇低氧(chronic intermittent hypoxia，CIH)对肝的损伤及其对肝CXC趋化因子配体10(CXC chemokine ligand-10，CXCL10)表达的影响，并探讨N-乙酰半胱氨酸(N-acetylcysteine，NAC)干预作用及机制。方法：21只健康雄性Spraque-Dawley大鼠随机分为正常对照组、慢性间歇低氧组(CIH组)和慢性间歇低氧+N-乙酰半胱氨酸组(CIH+NAC组)，每组7只。对照组置于空气循环舱内，其余两组置于间歇低氧舱内，每日8 h，共5周；对照组及CIH组每日均给予生理盐水灌胃，CIH+NAC组每日给予NAC溶液灌胃。5周后处死大鼠，测定大鼠肝组织MDA含量和SOD活力，采用HE染色法观察各组大鼠肝组织病理改变，免疫组织化学法比较各组大鼠肝CXCL10的表达水平。结果：与对照组相比，CIH组、CIH+NAC组大鼠肝MDA水平均升高(均P<0.05)，SOD活力均降低(均P<0.05)；与CIH组比较，CIH+NAC组大鼠肝MDA降低，SOD活力升高，差异均有统计学意义(均P<0.05)。与对照组比较，CIH组和CIH+NAC组大鼠肝脂肪变程度及炎症反应均增加(均P<0.01)；CIH+NAC组大鼠肝损伤较CIH组减轻(P<0.05)。与对照组相比较，CIH组和CIH+NAC组大鼠肝组织CXCL10表达均增强(均P<0.01)；CIH+NAC组较CIH组减弱(P<0.01)。结论：CIH可导致大鼠肝组织损伤，并使大鼠肝组织CXCL10表达增加；NAC可以减轻CIH导致的大鼠肝氧化应激和炎症反应，部分改善大鼠肝损伤。

Effect of chronic intermittent hypoxia on the expression of CXC chemokine ligand-10 in rat liver and the interventional effect of N-acetylcysteine

Objective: To explore the effect of chronic intermittent hypoxia (CIH) on liver injury and to examine the expression of liver CXC chemokine ligand-10 (CXCL10) in the rats, and to explore the effect of N-acetylcysteine (NAC). Methods: A total of 21 male SD rats were randomly divided into a control group, a CIH group and a CIH+NAC group (n=7 in each group). The control group exposed to normal gaseous environment, the other 2 groups were exposed to CIH for 5 weeks (8 h/d); the control group and the CIH group were given daily saline lavage, the CIH+NAC group daily received NAC solution. After the end of 5 weeks, the rats were killed, and the MDA content and SOD activity in rat liver tissues were detected. The liver sections were stained with hematoxylin-eosin (HE) and the liver pathology was observed. The expression of CXCL10 in the liver tissues was detected by immunohistochemical method. Results: Compared with the control group, the MDA levels in rat liver tissues were increased (P<0.05), and the SOD levels were decreased (P<0.05) in the CIH group and the CIH+NAC group. Compared with the CIH group, the SOD levels in the rat liver tissues were increased (P<0.05), and the MDA levels were decreased in the CIH+NAC group. Compared with the control group, the hepatic steatosis and inflammatory reactions were more severe in the CIH group and the CIH+NAC group (both P<0.01). Compared with the CIH group, the hepatic steatosis and inflammatory reactions were reduced in the CIH+NAC group (P<0.05). The liver damage in the CIH+NAC group was less than that in the CIH group (P<0.05). Compared with the control group, the CXCL10 expression in the CIH group and the CIH+NAC group was increased (both P<0.01). The CXCL10 expression in the CIH+NAC group was down-regulated compared with that in the CIH group (P<0.01). Conclusion: CIH can lead to liver injury and induce CXCL10 expression in rat liver tissues. The NAC can alleviate rat liver oxidative stress and inflammation caused by CIH, and in turn to improve the liver injury in rats.