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慢性间歇低氧对氧化应激和炎症反应的影响及脂联素的干预作用

Effects of chronic intermittent hypoxia on oxidative stress and inflammatory response and the interventional roles of adiponectin

摘要目的 探讨慢性间歇性低氧(CIH)对氧化应激和炎症反应的影响及脂联素的干预作用.方法 将45只雄性Wistar大鼠按随机数字表法随机分为:常氧对照组、CIH组和CIH-脂联素组各15只.常氧对照组呼吸正常空气,CIH组每天行8h的CIH,CIH-脂联素组除每天8h的CIH外,每周经尾静脉注射脂联素10 μg.35 d后采集所有大鼠的血液标本,比较三组间血清中脂联素、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6、C-反应蛋白(CRP)及颏舌肌组织中丙二醛、超氧化物歧化酶(SOD)、和髓过氧化物酶(MPO)、活性氧族和核因子(NF)-κB水平.结果 CIH组血清中脂联素水平均显著低于常氧对照组、CIH-脂联素组[(4 208±2 239)比(7 051 ±2 432)、(6 405 ±2 384) ng/ml,均P< 0.05],但与CIH-脂联素组(1.04±0.27)差异无统计学意义.CIH组血清TNF-α和CPR水平均显著高于常氧对照组、CIH-脂联素组[(70.87 ±35.16)比(26.54±20.32)、(29.50±22.54) pg/ml和(31.84±11.48)比(22.68 ±9.63)、(25.32 ±8.34) mg/L](均P<0.05),而常氧对照组、CIH-脂联素组间差异均无统计学意义;CIH组、CIH-脂联素组IL-6水平均显著高于常氧对照组[(30.54±12.25)、(23.04±13.85)比(14.10±8.83) pg/ml,均P<0.05],而CIH组、CIH-脂联素组组间差异无统计学意义.CIH组颏舌肌组织中丙二醛含量均显著高于常氧对照组、CIH-脂联素组[(8.05±4.53)比(5.18±3.03)、(5.74±3.06)nmol/mg,均P<0.01],常氧对照组、CIH-脂联素组间差异无统计学意义;CIH-脂联素组SOD活力水平显著低于CIH组而高于常氧对照组[(42.42 ±23.17)比(61.77±36.38)、(18.62±11.67) U/mg,均P<0.05];CIH组、CIH-脂联素组MPO含量均显著高于常氧对照组[(0.40±0.29)、(0.31±0.17)比(0.17 ±0.08) μU/mg,均P<0.01],而CIH组、CIH-脂联素组间差异无统计学意义;CIH-脂联素组活性氧族相对水平显著低于CIH组而高于常氧对照组(1.94±1.01比3.31 ±1.56、1.08 ±0.38,均P<0.05);CIH组NF-κB的mRNA相对量显著高于常氧对照组(2.24±0.34比0.78 ±0.21,P<0.05)但与CIH-脂联素组(1.04±0.27)差异无统计学意义.结论 CIH可诱导体内产生显著的氧化应激和炎症反应,NF-κB通路参与其中,脂联素对其有抑制作用.

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abstractsObjective To explore the effects of chronic intermittent hypoxia (CIH) on oxidative stress and inflammatory response and the interventional roles of adiponectin (Ad).Methods A total of 45 male Wistar rats were randomly divided into three groups of control group,CIH and CIH + Ad (n =15 each).The control group breathed room air while the CIH and CIH + Ad groups received CIH 8 h/d for 5 successive weeks.The CIH + Ad group Ad had an injection of 10 μg once a week through tail vein.At the end of experiment (Day 35),comparison was performed among three groups about Ad,tumor necrosis factor α (TNF-α),C-reactive protein (CRP) and interleukin (IL) 6 from serum as well as malondialdehyde,superoxide dismutase (SOD),myeloperoxidase (MPO),reactive oxygen spieces (ROS) and nuclear factor (NF) κB from genioglossus.Results Serum Ad level in CIH group was lower than those in control and CIH + Ad groups ((4 208 ± 2 239) vs (7 051 ± 2 432) and (6 405 ± 2 384) ng/ml,all P < 0.05) with no statistic difference between control and CIH + Ad groups.Both serum levels of TNF-α and CRP were higher in CIH group than those in control and CIH + Ad groups ((70.87 ± 35.16) vs (26.54 ± 20.32) and (29.50 ±22.54) pg/ml,as well as(31.84 ± 11.48) vs(22.68 ±9.63),(25.32 ± 8.34) mg/L,all P <0.05) with no significant difference between control and CIH + Ad groups.Serum IL-6 levels were all higher in CIH group and CIH + Ad group than that in control group ((30.54 ± 12.25) and (23.04 ± 13.) vs (14.10 ±8.83) pg/ml,all P <0.05) with no significant difference between CIH and CIH + Ad groups.Genioglossal malondialdehyde level was significantly elevated in CIH group than those in control and CIH +Adgroups ((8.05 ±4.53) vs (5.18±3.03) and((5.74±3.06) nmol/mg,all P<0.01) with no significant difference between control and CIH + Ad groups.Genioglossal SOD activity was lower in CIH +Ad group than that in CIH group but higher than that in control group((42.42 ± 23.17) vs (61.77 ±36.38) and (18.62 ± 11.67) U/mg,all P < 0.05).Genioglossal MPO levels were significantly higher in both CIH and CIH + Ad groups than that in control group ((0.40 ±0.29) and (0.31 ±0.17) vs (0.17 ±0.08) μU/mg,all P < 0.01),with no significance between CIH and CIH + Ad groups.The relative level of total reactive oxygen species (ROS) in genioglossus of CIH + Ad group was significantly lower than that in CIH group but higher than that in control group (1.94 ± 1.01 vs 3.31 ± 1.56 and 1.08 ± 0.38 all P <0.05).The transcription of NF-κB was significantly higher in CIH group than that in control and CIH + Ad groups (2.24 ± 0.34 vs 0.78 ± 0.21,P < 0.05),but there was no statistical difference with CIH + Ad group (1.04 ± 0.27).Conclusion CIH may induce oxidative stress and inflammation possibly through NF κB pathway while a supplement of Ad attenuates the above CIH-induced responses.

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中华医学杂志

中华医学杂志

2015年95卷16期

1218-1221页

MEDLINEISTICPKUCSCDCA

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