吡格列酮对慢性间歇性低氧大鼠氧化应激水平及胰岛功能的干预作用  

Effect of Pioglitazone on Oxidative Stress and Islet Function in Rats Suffered from Chronic Intermittent Hypoxia

作　　者：周燕[1] 陈静[1] 高一萍[1] 蔡珊珊[1] 薛欣欣[1] 

机构地区：[1]桂林医学院附属医院呼吸内科,广西桂林541001

出　　处：《中国药学杂志》2015年第5期408-412,共5页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(81460019);广西医疗卫生重点科研课题资助项目(2011007);广西自然科学基金资助项目(2013GXNSFAA019208)

摘　　要：目的研究吡格列酮对慢性间歇性低氧大鼠氧化应激水平及胰岛功能的干预作用。方法建立慢性间歇低氧大鼠模型,将SD雄性大鼠48只随机分为常氧对照组、慢性间歇低氧模型组、吡格列酮干预组,每组16只。慢性间歇低氧及吡格列酮组均循环给予氮气和氧气,常氧对照组组给予常氧对照。吡格列酮组给予吡格列酮10 mg·kg-1·d-1灌胃,慢性间歇低氧、常氧对照组组均予等量生理盐水灌胃。分别于实验4、8周末处死大鼠,观察各组大鼠血清肿瘤坏死因子α、丙二醛、谷胱甘肽过氧化物酶、8-异前列腺素、超氧化物歧化酶、胰岛β细胞功能指数及胰腺组织核转录因子mRNA的表达情况。结果与常氧对照组组比较,慢性间歇低氧组大鼠血清肿瘤坏死因子-α、丙二醛、8-异前列腺素及胰腺组织核转录因子mRNA表达水平均升高,谷胱甘肽过氧化物酶、超氧化物歧化酶及胰岛β细胞功能指数均降低(P<0.05或P<0.01),且慢性间歇低氧8周组比4周组变化更明显(P<0.05或P<0.01),吡格列酮4组肿瘤坏死因子-α、丙二醛、8-异前列腺素及胰腺组织核转录因子mRNA表达水平均升高,谷胱甘肽过氧化物酶、超氧化物歧化酶及胰岛β细胞功能指数均降低(P<0.05),吡格列酮8周组差异无统计学意义(P>0.05);与慢性间歇低氧组比较,吡格列酮组血清肿瘤坏死因子-α、丙二醛、8-异前列腺素及胰腺组织核转录因子mRNA表达水平均降低,谷胱甘肽过氧化物酶、超氧化物歧化酶及胰岛β细胞功能指数升高(P<0.05或P<0.01),且吡格列酮8周组比4周组变化更明显(P<0.05或P<0.01)。结论慢性间歇低氧可导致大鼠氧化应激及胰岛β细胞功能降低,吡格列酮能通过抑制核转录因子核转位降低氧化应激水平,改善慢性间歇低氧状态下胰岛功能,且呈现一定的时间依赖性。OBJECTIVE To investigate effects of pioglitazone on oxidative stress and islet function in rats suffered from chro- nic intermittent hypoxia. METHODS A chronic-intermittent hypoxia model in rats was established. Forty-eight male SD rats were randomly assigned into three experimental groups（ n = 16/group） , normoxia control group, chronic intermittent hypoxia mod- el group,and pioglitazone intervention group. Rats in NC group were raised normally, while rats in CIH and pioglitazone group were exposed to alternative cycles of O2and N：. Rats in pioglitazone group were fed with pioglitazone （ 10 mg · kg-1· d-1 ） by garaged, and both the CIH and NC groups were treated with isovolume normal saline solution（ NS）. The rats were sacrificed at 4 and 8 weeks and changes were detected about tumor necrosis factorcL, malondialdehyde, glutathione peroxidase, 8-iso-prostaglan- din F2α, superoxide dismutase in serum as well as HOMA-β and the expression of nuclear transcription factor-KB mRNA in pan- creas tissue. RESULTS Compared with NC group,the level of TNF-α, MDA, 8-iso-PGF2α in serum and expression of NF-KB mRNA increase, GSH-Px, SOD and HOMA-β declines in CIH group（ P 〈 0.05 or P 〈 0.01 ） , and the above indicators in CIH 8 group change more significantly than those in CIH 4 group（ P 〈 0.05 or P 〈 0.01 ） ; pioglitazone 4 group shows a higher expres- sion of TNF-α, MDA, 8-iso-PGF2α and NF-κB mRNA and a lower expression of GSH-Px, SOD and HOMA-β（ P 〈 0.05 ） , while there are no significance in pioglitazone 8 group compared to NC group（ P 〉 0.05 ）. Compared with CIH group, the level of TNF-α, MDA and 8-iso-PGF2α in serum and expression of NF-κB mRNA in pancreas tissue decline, GSH-Px, SOD and HOMA- β rises in pioglitazone rats （P 〈 0.05 or P 〈 0.01 ） , and those detections in pioglitazone 8 group show more remarkable changes than rats in pioglitazone 4 group（ P 〈 0.05 or P 〈 0.01 ）. CONCLUSION The condition of CIH results in oxidative stress and islet β

关 键 词：慢性间歇性低氧 氧化应激 胰岛功能 吡格列酮 核转录因子 

分 类 号：R965[医药卫生—药理学]