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IKK-NBD多肽通过调节c-rel对抗局灶脑缺血再灌注大鼠大脑皮质炎症反应
  • ISSN号:1000-5404
  • 期刊名称:《第三军医大学学报》
  • 时间:0
  • 分类:R364.5[医药卫生—病理学;医药卫生—基础医学] R743.31[医药卫生—神经病学与精神病学;医药卫生—临床医学]
  • 作者机构:[1]重庆医科大学附属第一医院神经内科,重庆400016
  • 相关基金:教育部“高等学校博士学科点专项科研基金”联合资助课题(20095503110001);重庆市卫生局中医药科研项目(2012-2-128)
中文摘要:

目的探讨局灶脑缺血再灌注大鼠不同时间点大脑皮质炎症反应及IKK-NBD多肽干预对抗炎症反应的机制。方法采用线栓法制备Spragne-Dawley(SD)大鼠局灶脑缺血再灌注模型。将大鼠分为假手术组、模型组及IKK.NBD组,再下设再灌注1d和7d2个时相点。IKK-NBD组通过侧脑室定位定量注入4μIKK.NBD。对各组进行Zea-Longa神经功能评分,HE染色观察病理变化,Westernblot与荧光定量PT-PCR分别检测缺血皮质区c-rel蛋白和IKappaBot(IKBct)mRNA表达,ELISA检测缺血区炎症因子IL-1B和IL-10的含量。结果①再灌注1、7d时,IKK-NBD对模型大鼠行为学改善明显;②再灌注1、7d时,模型组病理改变较IKK-NBD组明显;③胞核c-rel蛋白:再灌注1、7d时,模型组均高于假手术组(P〈0.05);再灌注1d时,IKK-NBD组高于假手术组(P〈0.05);再灌注1、7d时,IKK-NBD组低于模型组(P〈0.05,P〈0.01);随着时间延长模型组和IKK-NBD组均降低(P〈0.01);④IKBotmRNA:再灌注1、7d时,模型组和IKK-NBD组均高于假手术组(P〈0.05),7d较1d回落;再灌注1d时,IKK-NBD组高于模型组(P〈0.01);⑤IL-1p:再灌注1、7d时,模型组与IKK-NBD组均明显高于假手术组(P〈0.01),浓度随时间降低;再灌注1d时,IKK-NBD组较模型组减少(P〈0.01);IL-10:再灌注l、7d时,模型组与IKK-NBD组均明显高于假手术组(P〈0.01),浓度随时间降低;再灌注1、7d时,IKK-NBD组均高于模型组(P〈0.01)。结论IKK—NBD在局灶脑缺血再灌注损伤后早期可以通过上调IKBot限制c-rel入核,下调IL-1B,上调IL-10而减轻再灌注后炎症损伤;而脑缺血再灌注恢复期,少量c-rel可上调IL-10起到抗炎作用。

英文摘要:

Objective To investigate the cerebral cortex inflammation of SD rats model of focal cerebral ischemia/reperfusion and the underlying mechanism of IKK-NBD peptides' anti-inflammation effect. Methods The MCAO/R SD rats were randomly assigned to 3 groups, that is, sham operation group, model group and IKK-NBD group, and each group was further randomly divided into 2 subgroups with reperfusion 1 and 7 d after 2 hours' ischemia. IKK-NBD of 4 μL was injected into the right lateral ventricle in 2 h before model infliction. Neurobehavior was evaluated by Zea-Longa score. HE staining was used for pathological observation, Western blotting and quantitative RT-PCR for mRNA and protein expression levels of c-rel and IkappaBet (Is:Bet), and ELISA for the contents of IL-β and IL-10 in the isehemic cortex. Results IKK- NBD improved the behavioral recovery and reduced edema and necrosis after 1 and 7 d of reperfusion. The protein expression of c-rel in the cell nucleus was significantly higher in the model group than in the sham operation group (P 〈 0.05), but significantly lower in IKK-NBD group than model group in 1 and 7 d after reperfusion (P 〈 0. 05, P 〈 0. 01 ), while, in 1 d after reperfusion, it was significantly higher in IKK-NBD group than the sham operation group (P 〈 0. 05 ). It was continuously decreased in the IKK-NBD group and model group with the elapse of time (P 〈 0. 05 ). Expression level of Is:Bet mRNA was significantly higher in the model and IKK- NBD groups than the sham operation group in 1 and 7 d after reperfusion (P 〈 0. 05 ), with that in day 7 lower than in day 1, and it was higher in IKK-NBD group than in model group in 1 d after reperfusion (P 〈0. 01 ).IL-1β and IL-IO were significantly higher in the model and IKK-NBD groups than the sham operation group in 1 and 7 d after reperfusion (P 〈 0. 01 ), and continued to reduce with the time, but in the day 1, IL-1β was lower in the IKK-NBD group than in the model group (P 〈0. 01 ), and IL-

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期刊信息
  • 《第三军医大学学报》
  • 北大核心期刊(2011版)
  • 主管单位:第三军医大学
  • 主办单位:第三军医大学
  • 主编:钱桂生
  • 地址:重庆市沙坪坝区高滩岩30号第三军医大学学报编辑部
  • 邮编:400038
  • 邮箱:aammt@mail.tmmu.com.cn
  • 电话:023- 68752187
  • 国际标准刊号:ISSN:1000-5404
  • 国内统一刊号:ISSN:50-1126/R
  • 邮发代号:78-91
  • 获奖情况:
  • 先后20余次获全国、全军、教育部和省、市优秀科技...,2003年、2005年两度被评为"国家期刊奖百种重点科...
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  • 被引量:47530