山东大学耳鼻喉眼学报 ›› 2017, Vol. 31 ›› Issue (1): 45-49.doi: 10.6040/j.issn.1673-3770.0.2017.027

• 论著 • 上一篇    下一篇

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

李小波1,曹忠胜1,辛洁1,谢辰1,陈锐2   

  1. 苏州大学附属第二医院, 1.耳鼻咽喉头颈外科;
    2.睡眠中心, 江苏 苏州 215004
  • 收稿日期:2017-01-17 出版日期:2017-02-16 发布日期:2017-02-16
  • 通讯作者: 曹忠胜. E-mail:cao4018@163.com

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

  1. 1. Department of Otolaryngology &Head and Neck Surgery;2. Sleep Center, the Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, China
  • Received:2017-01-17 Online:2017-02-16 Published:2017-02-16

摘要: 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。

关键词: 认知功能, 睡眠呼吸暂停,阻塞性, 间歇性低氧, 氧化应激

Abstract: 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 low dose 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 agonist-rosiglitazone can improve the oxidative stress damage and cognitive dysfunction induced by intermittent hypoxia in mice.

Key words: Oxidative stress, Sleep apnea, obstructive, Cognitive function, Intermittent hypoxia

中图分类号: 

  • R766.7
[1] 李涛平. 阻塞性睡眠呼吸暂停低通气综合征与多器官疾病的关系[J].中华肺部疾病杂志(电子版),2011,4(4):259-264. LI Taoping. Relationship between obstructive sleep apnea hypopnea syndrome and multiple organ disease[J]. Chin J Lung Dis(Elec Ed), 2011, 4(4):259-264.
[2] Yamauchi M, Kimura H. Oxidative stress in obstructive sleep apnea: putative pathways to the cardiovascular complications[J]. Antioxid Redox Signal, 2008,10(4):755-768.
[3] Hong S, Xin Y, HaiQin W, et al. The PPARγ agonist rosiglitazone prevents cognitive impairment by inhibiting astrocyte activation and oxidative stress following pilocarpine-induced status epilepticus[J]. Neurol Sci 2012,33(3):559-566.
[4] Chen T, Jin X, Crawford BH, et al. Cardioprotection from oxidative stress in the newborn heart by activation of PPARγ is mediated by catalase[J]. Free Radic Biol Med,2012,53(2):208-215.
[5] 王彤宇, 吴广才, 孙冬霞, 等. 吡格列酮治疗血管性认知功能障碍的临床观察[J].中华老年心脑血管病杂志,2013,15(11):1174-1177. WANG Tongyu, WU Guangcai, SUN Dongxia, et al. Application of pioglitazone in treatment of vascular cognitive impairment[J]. Chin J Geria Heart Brain Vessel Dis, 2013, 15(11):1174-1177.
[6] Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory[J]. Nat Protoc, 2006, 1(2):848-858.
[7] 王青云, 陈锐, 曹忠胜, 等. 同期多平面手术对中青年中-重度OSAHS患者血清氧化应激水平和认知功能的影响[J].临床耳鼻咽喉头颈外科杂志,2015,29(24): 2139-2142. WANG Qingyun, CHEN Rui, CAO Zhongsheng, et al. Effects of simultaneous multi-level surgery intervention on the changes of the oxidative stress and cognitive function in young and middle-aged patients with Moderate-severe obstructive sleep apnea hypopnea syndrome[J]. J Clin Otorhinolaryngol Head Neck Surg, 2015, 29(24): 2139-2142.
[8] Tauman R, Lavie L, Greenfeld M, et al. Oxidative stress in children with obstructive sleep apnea syndrome[J]. J Clin Sleep Med, 2014,10(6):677-681.
[9] 李亚男, 陈锐, 刘辉玉, 等. 间歇低氧小鼠血清氧化应激指标的变化及N-乙酰半胱氨酸的治疗作用[J].江苏医药,2011,37(4):387-389. LI Yanan, CHEN Rui, LIU Huiyu, et al. The changes of serum oxidative stress indexes of mice exposed to intermittent hypoxia and the therapeutical effect of N-acetylcysteine[J]. Jiangsu Med J, 2011, 37(4):387-389.
[10] 琚静美, 陈锐, 王婧, 等. 慢性间歇低氧诱导小鼠学习记忆障碍的实验研究[J]. 中华肺部疾病杂志(电子版),2014,7(6):10-13. JU Jingmei, CHEN Rui, WANG Jing, et al. Experimental study on the impairment of spatial learning and memory in the mice exposed to chronic intermittent hypoxia[J]. Chin J Lung Dis(Elec Ed), 2014, 7(6):10-13.
[11] Yu X, Shao XG, Sun H, et al. Activation of cerebral peroxisome proliferator-activated receptors gamma exerts neuroprotection by inhibiting oxidative stress following pilocarpine-induced status epilepticus[J]. Brain Res, 2008, 1200:146-158.
[12] Murphy GJ, Holder JC. PPAR-gamma agonists: therapeutic role in diabetes, inflammation and cancer[J]. Trends Pharmacol Sci, 2000, 21(12):469-474.
[13] Collino M, Aragno M, Mastrocol R, et al. Modulation of the oxidative stress and inflammatory response by PPAR-gamma agonists in the hippocampus of rats exposed to cerebral ischemia/reperfusion[J]. Eur J Pharmacol, 2006, 530(1-2):70-80.
[14] 罗颜, 曹忠胜, 朱政文, 等. 15D-PGJ2对小鼠耳蜗基底膜螺旋神经节氧化损伤的防护作用[J].中华耳科学杂志,2015,13(1):71-75. LUO Yan, CAO Zhongsheng, ZHU Zhengwen, et al. Protective effect by 15D-PGJ2 against oxidative damage to mouse cochlear spiral ganglion[J]. Chin J Otol, 2015, 13(1):71-75.
[15] 王宁, 韩晶, 徐艳炜, 等. 过氧化氢损伤原代皮质神经元中PPARγ的改变[J].中华医学杂志,2015,95(21):1686-1690. WANG Ning, HAN Jing, XU Yanwei, et al. Hydrogen peroxide-induced changes of PPARγ in primary cultured cortical neurons[J]. Nat Med J Chin, 2015, 95(21):1686-1690.
[16] 姜云苓, 李广群, 沈洁, 等. 罗格列酮对慢性阻塞性肺疾病大鼠模型肺组织氧化应激的影响[J].中国老年学杂志,2015,35(7):1893-1894. JIANG Yunling, LI Guangqun, SHEN Jie, et al. Effects of rosiglitazone on oxidative stress in lung tissue of rats with chronic obstructive pulmonary disease[J]. Chin J Gerontol, 2015, 35(7):1893-1894.
[18] Hwang J, Kleinhenz DJ, Lassegue B, et al. Peroxisome proliferator-activated receptor-gamma ligands regulate endothelial membrane superoxide production[J]. Am J Physiol Cell Physiol, 2005, 288(4):C899-905.
[19] Jennings JS, Gerber AM, Vallano ML. Pharmacological strategies for neuroprotection in traumatic brain injury[J]. Mini Rev Med Chem, 2008, 8(7):689-701.
[20] 邓永兵, 唐文渊. PPARγ的神经保护作用研究进展[J].中华神经外科疾病研究杂志,2010,9(1):92-94. DENG Yongbing, TANG Wenyuan. Research progress on neuroprotection of PPAR-gamma[J]. Chin J Neurosurg Dis Res, 2010, 9(1):92-94.
[21] Searcy JL, Phelps JT, Panncani T, et al. Long-term pioglitazone treatment improves learning and attenuates pathological markers in a mouse model of Alzheimers disease[J]. J Alzheimers Dis, 2012, 30(4):943-961.
[1] 王红梅,李连贺. 神经心理量表联合事件相关电位对中、重度阻塞性睡眠呼吸[J]. 山东大学耳鼻喉眼学报, 2018, 32(2): 56-61.
[2] 耿聪,张丽伟,丁明. 全身麻醉对单纯鼾症患者术后认知功能的影响[J]. 山东大学耳鼻喉眼学报, 2017, 31(5): 85-88.
[3] 张转,刘涛,白治丽,周长明. 氧化应激与噪音性聋发病机制及治疗进展[J]. 山东大学耳鼻喉眼学报, 2017, 31(5): 101-103.
[4] 李延忠. 肥胖与阻塞性睡眠呼吸暂停[J]. 山东大学耳鼻喉眼学报, 2016, 30(5): 1-4.
[5] 朱越,黄志纯,杨明,朱新. 阻塞性睡眠呼吸暂停低通气综合征患者认知功能损害的研究[J]. 山东大学耳鼻喉眼学报, 2016, 30(5): 68-74.
[6] 李兰根, 伟伟, 张玉凤, 格日乐图, 杨佳, 张艳梅. SIRT1抗视网膜色素上皮细胞氧化应激作用的实验研究[J]. 山东大学耳鼻喉眼学报, 2015, 29(6): 56-59.
[7] 毕宏生,李树杰,崔 彦,王 慧 . 茶多酚防治STZ诱导的大鼠糖尿病性白内障的机制[J]. 山东大学耳鼻喉眼学报, 2008, 22(1): 1-05 .
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!