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人参皂苷Rb1激活Nrf2/ARE通路对术后疲劳综合征老年大鼠骨骼肌氧化应激损伤的影响
引用本文:毛翔宇,庄成乐,陈伟哲,刘舒,朱江,吴天添,张昌静,陈必成,余震. 人参皂苷Rb1激活Nrf2/ARE通路对术后疲劳综合征老年大鼠骨骼肌氧化应激损伤的影响[J]. 医学研究杂志, 2014, 43(5): 26-30
作者姓名:毛翔宇  庄成乐  陈伟哲  刘舒  朱江  吴天添  张昌静  陈必成  余震
作者单位:[1]温州医科大学附属第一医院胃肠外科,325000 [2]温州医科大学附属第一医院外科学实验室,325000 [3]同济大学附属第十医院(上海市第十人民医院)普外科,上海200072
基金项目:国家自然科学基金资助项目(81171857)
摘    要:目的研究人参皂苷Rb1激活Nrf2/ARE通路来减轻术后疲劳综合征老年大鼠骨骼肌氧化应激损伤,探讨人参皂苷Rb1的抗疲劳机制。方法以70%中段小肠切除用以制备术后大鼠疲劳综合征模型。老年SD大鼠随机分为对照组、模型组和人参皂苷Rb1干预组,每组再分别按时间点分为术后6h,第1、3、7天组。在术后对应时间点进行旷场实验检测行为学变化后取骨骼肌,分光光度法测超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量,RT—PCR检测Nrf2及下游Ⅱ相解毒酶基因Nqol表达。Westernblot检测Nrf2核转位情况。结果旷场实验显示,相比于对照组,模型组术后穿越格子数降低(第1、3天,P〈0.05),休息时间增加(第1、3、7天,P〈0.05);相比于模型组,干预组穿越格子数术后增加(第1、3天,P〈0.05)。相比于对照组,模型组SOD活性在术后增加(第3、7天,P〈0.05),MDA含量增加(第1、3、7天,P〈0.05);相比于模型组,干预组SOD活性术后增加(第3、7天,P〈0.05),MDA含量术后降低(第3、7天,P〈0.05)。RT—PCR结果表明,相比于对照组,模型组Nrf2术后表达增加(第1、3天,P〈0.05),Nqol术后表达有上升倾向(第1、3天,P〉0.05);相比于模型组,干预组Nrf2术后表达增加(6h、第1天、第3天,P〈0.05),Nqol表达增加(6h、第1天,P〈0.05)。Westernblot结果表明,相比于对照组,模型组核内Nrf2术后表达增加(6h、第1、3、7天,P〈0.05);相比于模型组,干预组核内Nrf2术后表达增加(6h、第1天、第3天,P〈0.05)。结论通过激活Nrf2/ARE通路,人参皂苷Rb1能减轻老年大鼠术后疲劳综合征骨骼肌氧化应激所致损伤,这可能是其抗术后疲劳的一种机制。

关 键 词:人参皂苷Rb1  术后疲劳综合征  Nrf2  ARE信号通路  老年大鼠  氧化应激

Effects of Ginsenoside Rbl on the Oxidative Stress in the Skeletal Muscles of Elderly Rats with Postoperative Fatigue Syndrome via Nrf2 - ARE Activation
Affiliation:Mao Xiangyu,Zhuang Chengle, Chen Weizhe,et al. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang 325000, China
Abstract:Objective To investigate the effects of ginsenoside Rbl on the oxidative stress in the skeletal muscles of elderly rats with postoperative fatigue syndrome (POFS) via the activation of Nrf2/ARE signal pathway and the antifatigue mechanism of ginsengsides Rbl. Methods We chose resection of 70% of the "middle" small intestine as the rat model for POFS. Elderly male SD rats were randomly di- vided into control group (group C) , POFS model group (group P) and ginsengoside Rbl intervention group (group G) , and each group were divided into subgroups by postoperative 6 hours and 1,3,7 days. The skeletal muscles were removed at each time point after open field test (OFT) to detect the activities of superoxide dismutase (SOD) and the contents of malondealdehyde (MDA) , to detect the levels of nuclear factor erythroid2 - related factor (Nrf2) , and the phase Ⅱ detoxifying enzyme gene NADP ( H ) : ( quinine oxidoreductasel ( Nqol ) mRNA by Real - time PCR. Nrf2 translocation was detected by Western blot. Results In open - field test, compared with group C, total journey of group P decreased ( day 1 , day 3, P 〈 0.05 ) , resting time increased ( day 1, day 3, day 7,P 〈 0.05 ). Compared with the group P, total journey of group G increased (day 1 , day 3, P 〈 O. 05 ). Compared with the group C, the activities of superoxide dis- mutase (SOD) of group P increased ( day 3, dat 7,P 〈 0.05 ) and the contents of malondealdehyde (MDA) increased( day 1 , day 3, day 7, P 〈 0.05 ). Compared with the group P, the SOD of group P increased ( day 3, day 7, P 〈 0.05 ) and MDA decreased ( day 3, day 7, P 〈 0.05).Compared with group C, level ofNrf2 mRNA of group P increased (day 1, day3, P〈0.05), level of Nqol mRNA of group P had an upward trend ( day 1 , day 3, P 〉 0.05 ) without statistical significance. Compared with the group P, level of Nrf2 mRNA of group G inereased(6h,day 1, day 3, P 〈0.05),level of Nqol mRNA of group G increased(6h,day 1, P 〈0.05). Compared with the group C,nucleus protein of Nrf2 of group P increased (6h, day 1, day 3, day 7,P 〈 0.05 ). Compared with the group P, nucleus protein of Nrt2 of group G increased (6h,day 1, day 3,P 〈 0.05). Conclusion Ginsenoside Rbl could reduce the oxidative stress mediated injury in the skeletal muscles in erlderly rats with POFS via Nrf2/ARE signal pathway,which may be one of the mechanisms against POFS.
Keywords:Ginsenoside Rbl  Postoperative fatigue syndrome  Nrf2/ARE signal pathway  elderly rat  Oxidative stress
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