古强,王晨宇,马延超.运动预适应通过上调PTEN表达改善实验性溃疡性结肠炎小鼠炎症反应[J].北京体育大学学报,2017,40(12):55-63+71.
运动预适应通过上调PTEN表达改善实验性溃疡性结肠炎小鼠炎症反应
Exercise Preconditioning Improves the Inflammatory Reaction of Experimental Ulcerative Colitis in Mice by Up Regulation of PTEN Expression
投稿时间:2017-02-01  
DOI:10.19582/j.cnki.11-3785/g8.2017.12.010
中文关键词:  关键词:运动预适应  PTEN  溃疡性结肠炎  炎症反应  NF-κB  信号转导
英文关键词:Keywords: exercise preconditioning  PTEN  ulcerative colitis  inflammatory reaction  NF-κB  signal transduction
基金项目:基金项目:河南省科技攻关重点项目(编号:142102310359);河南省科技计划资助项目( 编号: 122300410257)。通信作者:马延超。
作者单位
古强 中国矿业大学江苏 徐州 221116 
王晨宇 郑州航空工业管理学院河南 郑州 450015 
马延超 洛阳师范学院河南 洛阳 471022 
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中文摘要:
      摘要:目的:观察8周运动预适应对葡聚糖硫酸钠(DSS)诱导的实验性溃疡性结肠炎(UC)小鼠模型炎症反应的影响并探讨第10号染色体同源丢失性磷酸酶张力蛋白(PTEN)在其中的作用与机制。方法:雄性C57BL/6小鼠随机分为安静组、运动组以及运动+抑制剂组,运动组进行8周转轮运动,运动+抑制剂组在运动同时给予PTEN选择性抑制剂phen腹腔注射。8周后每组按照是否进行UC造模再分为造模组和相应的对照组:安静对照组(RC)、安静造模组(RM)、运动对照组(EC)、运动造模组(EM)、运动+抑制剂对照组(EIC)以及运动+抑制剂造模组(EIM)。每天观察记录小鼠临床症状并进行疾病活动指数(DAI)评分;ELISA法测定血清淀粉样蛋白A(SAA)含量和结肠NF-κB活性;HE染色于光镜下观察结肠组织病理学变化并进行炎症评分;比色法测定结肠髓过氧化物酶(MPO)活性;实时荧光定量PCR检测IL-1β、IL-6、TNF-α和PTEN mRNA表达量;免疫印迹法测定PTEN、PI3K、Akt、I-κB和NF-κB p65蛋白表达量。结果:与RC组比较,RM组小鼠出现明显结肠炎症状(腹泻、便血等),DAI和炎症评分增加,SAA含量、结肠MPO活性以及炎症因子IL-1β、IL-6和TNF-α表达量升高,PTEN表达下调,PI3K/Akt/NF-κB信号途径明显激活。与RM组比较,EM组小鼠结肠炎症状减轻,DAI和炎症评分下降,SAA含量、结肠MPO活性以及炎症因子IL-1β和IL-6表达量降低,PETN表达上调,PI3K/Akt/NF-κB信号途径受到抑制。EM组的上述效应被PTEN抑制剂phen所逆转,即EIM组结肠炎临床表现以及各分子生物学指标与RM组趋近。结论:长期运动预适应通过上调PTEN表达抑制DSS诱导的实验性UC小鼠PI3K/Akt/ NF-κB信号转导通路进而改善全身及肠道炎症反应。
英文摘要:
      Abstract: Objective: The present study aimed to detect the effect of 8-week exercise preconditioning on inflammatory reaction of experimental ulcerative colitis (UC) induced by dextran sulfate sodium (DSS), and to explore the role and mechanism of phosphatase and tensin homolog detected on chromosome ten (PTEN). Methods: Male C57BL/6 mice were randomly assigned to rest, exercise and exercise plus inhibitor groups, exercise group’s mice performed 8-week wheel running, exercise plus inhibitor group’s mice finished the exercise and were injected PTEN selective inhibitor, phen. After 8 weeks, each group was divided into model group and corresponding control group according to whether the UC model was made, including rest control (RC), rest modeling (RM), exercise control (EC), exercise modeling (EM), exercise inhibitor control (EIC) and exercise inhibitor modeling (EIM) groups. Symptoms were detected and recorded daily, and evaluated by disease activity index (DAI), serum amyloid A (SAA) content and NF-κB activity were measured by ELISA, the histopathological change of the colon tissue with HE staining was observed by light microscope and carried out inflammation score; colon myeloperoxidase (MPO) activity was tested by colorimetry; the mRNA of IL-1β, IL-6, TNF-α and PTEN was detected by real-time PCR; proteins of PTEN, PI3K, Akt, I-κB and NF-κB p65 were explored by immunoblotting. Results: Compared with RC group, mice of RM group showed obvious colonitis symptoms (diarrhea, hemafecia, etc.), DAI and inflammation score increased, SAA content, colonic MPO activity and IL-1β, IL-6 and TNF-α expressions increased, PTEN gene expression decreased, and PI3K/Akt/NF-κB signal pathway was active. Compared with RM group, mice of EM group displayed less colonitis symptom and their DAI and inflammation scores decreased, SAA content, colonic MPO activity and IL-1β and IL-6 expressions decreased while PTEN gene expression increased, and PI3K/Akt/NF-κB signal pathway was inhabited. Above effects of EM group were reversed by PTEN inhibitor, i.e. the clinical manifestation of colonitis and molecular biological markers in EM group were similar as those in RM group. Conclusion: Long-term exercise preconditioning inhabits PI3K/Akt/NF-κB signal transduction pathway and improved systematic and intestinal inflammatory reaction via increase of PTEN gene expression in UC mice.
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