罗格列酮对间歇性低氧小鼠氧化应激及认知功能的作用研究

Effects of rosiglitazone on oxidative stress and cognitive function in mice exposed to intermittent hypoxia

目的研究PPARγ激动剂罗格列酮对间歇性低氧小鼠氧化应激及认知功能的作用。方法将60只小鼠随机分为常氧对照组(UC组,n=12)、单纯间歇性低氧组(IH组,n=12)、低剂量罗格列酮干预组(1 mg/kg ROS+IH组,n=12)、中剂量罗格列酮干预组(3 mg/kg ROS+IH组,n=12)、高剂量罗格列酮干预组(9 mg/kg ROS+IH组,n=12),IH组及罗格列酮灌胃处理后的各组小鼠置于间歇性低氧舱内给予间断通气,每天8 h。干预4周后,实验动物分两批,一批使用丙二醛(MDA)及超氧化物岐化酶(SOD)试剂盒测定各组小鼠血清MDA及SOD浓度;另一批使用Morris水迷宫检测各组小鼠学习记忆功能。结果 1与UC组相比,IH组血清MDA浓度升高(P<0.05),SOD浓度降低(P<0.05);与IH组相比,罗格列酮处理后的各组MDA浓度呈剂量依赖性降低(P<0.05),SOD浓度升高(P<0.05)。2水迷宫结果:与UC组相比,IH组水迷宫测试潜伏期延长、穿台次数减少、在平台象限所占时间百分比减小(P<0.05);与IH组相比,9 mg/kg ROS+IH组逃避潜伏期缩短、穿台次数增多、在平台象限所占时间百分比增大(P<0.05)。结论间歇性低氧能导致小鼠氧化应激损伤及认知功能障碍,PPARγ激动剂罗格列酮能够改善间歇性低氧引起的氧化应激损伤及认知功能障碍。

Objective To study the effects of PPAR gamma agonist rosiglitazone on the oxidative stress and cognitive functionon in mice exposed to intermittent hypoxia. Methods Sixty healthy male ICR mice were randomly divided into ： the normoxic control group（ UC group,n = 12）,the intermittent hypoxia group（ IH group,n = 12）,the lowdose of rosiglitazone intervention group（ 1 mg / kg ROS ＋ IH group,n = 12）,the middle dose of rosiglitazone intervention group（ 3 mg / kg ROS ＋ IH group,n = 12）,and the high dose of rosiglitazone intervention group（ 9 mg / kg ROS ＋ IH group,n = 12）. IH group and groups treated with rosiglitazone were exposed to intermittent hypoxia cabin with discontinuous gas,eight hours each day. After four weeks intervention,mice were divided into two parts. The MDA and SOD assay kits were used to measure MDA and SOD concentration of mice in part one and Morris water maze test was used to detect the learning and memory function of the remaining mice. Results Compared with the UC group,the MDA concentration increased（ P〈0. 05） and the SOD concentration decreased（ P〈0. 05） in the IH group; compared with IH group,MDA concentration of the groups treated with rosiglitazone decreased in a dose-dependent manner（ P〈0. 05） and SOD concentration increased. Compared with group UC,the average escape latency became longer,the times of crossing the platform and the time percentage spent in the platform quadrant reduced in the IH group; compared with the IH group,average escape latency shortened,frequency of crossing the platform and the percentage of time spent in platform quadrant increased in the 9 mg / kg ROS ＋ IH group（ P〈0. 05）. Conclusion PPAR gamma agonistrosiglitazone can improve the oxidative stress damage and cognitive dysfunction induced by intermittent hypoxia in mice.