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基于Toll样受体2/核转录因子kappa B通路探讨电针对脑缺血损伤大鼠的作用机制 被引量:15

Effect of electroacupuncture on neurological deficit and activity of TLR2/NF-κB signaling in cerebral ischemia/reperfusion injury rats
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摘要 目的:探讨电针是否通过影响Toll样受体2/核转录因子kappa B(TLR2/NF-κB)信号通路以减轻脑缺血再灌注损伤。方法:SD大鼠随机分为空白组、假手术组、模型组、电针组和电针+抑制剂组,每组24只。参照Longa改良线栓法制备大脑中动脉栓塞(MCAO)模型。电针组以电针刺激大鼠"水沟""内关""三阴交""委中"穴,每次30 min,1次/d,共28d;电针+抑制剂组以NF-κB抑制剂PDTC腹腔注射后(120mg/kg)再行电针刺激,1次/d,共28d。治疗第3、7、14、28天后,分别对各组大鼠进行神经行为学评分,实时荧光定量PCR法检测缺血半暗带区脑组织中TLR2、白细胞介素-1受体相关激酶(IRAK)、NF-κB mRNA的表达。结果:治疗后4个时间点,模型组、电针组及电针+抑制剂组神经行为学评分均呈逐渐下降趋势。与模型组比较,电针组在第3、7、28天时神经行为学评分明显降低(P<0.05),电针+抑制剂组在治疗后4个时间点神经行为学评分均明显降低(P<0.05)。与电针组比较,电针+抑制剂组在治疗后4个观察时间点的神经行为学评分均降低,但差异无统计学意义(P>0.05)。与空白组比较,模型组TLR2mRNA表达在4个观察时间点均明显升高(P<0.05),IRAK mRNA表达在第3、7天时升高(P<0.05),NF-κB mRNA表达在第3、7、14天时明显升高(P<0.05)。与模型组比较,电针组TLR2mRNA、NF-κB mRNA表达在第3、7、14天时明显下降(P<0.05),IRAK mRNA表达虽在第3天时下降(P<0.05),但在第14、28天时表达上升(P<0.05);电针+抑制剂组TLR2 mRNA、NF-κB mRNA表达在4个观察点均明显下调(P<0.05),IRAK mRNA表达在第3天时下降(P<0.05)。与电针组比较,电针+抑制剂组TLR2mRNA表达在第28天时下降(P<0.05),IRAK mRNA表达在第3、14、28天时明显下降(P<0.05),NF-κB mRNA表达在第3、7、14天时明显下降(P<0.05)。结论:电针刺激能改善缺血再灌注损伤大鼠神经缺损症状,延迟IRAK表达高峰,其机制可能与电针抑制TLR2/NF-κB信号通路活性� Objective To observe the effect of electroacupuncture(EA)on neurological behavior and activity of Tolllike receptor 2/nuclear factor kappa B(TLR2/NF-κB)signaling of the ischemic cerebral area in cerebral ischemia-reperfusion injury(CIRI)rats,so as to explore its mechanisms underlying improvement of CIRI.Methods A total of 120 male SD rats were randomly divided into blank control,sham operation,model,EA and EA+NF-κB inhibitor(Pyrrolidine Dithiocarbamate Hydrochloride,PDTC,EA+PDTC)groups which were further divided into 3,7,14 and 28 dsubgroups(n=6 in each subgroup).The CIRI model was established by occlusion of the middle cerebral artery for 90 min,followed by reperfusion.EA(1-20 Hz,6 V)was applied to'Shuigou'(GV26),'Neiguan'(PC6),'Sanyinjiao'(SP6)and'Weizhong'(BL40)for 30 min,once a day for 28 days.For rats of the EA+PDTC group,PDTC solution(120 mg/kg)was intraperitoneally injected on the 3 rd day after successful modeling and before EA intervention.The neurological deficit severity(Zea Longa score)was assessed 3,7,14 and 28 days after modeling.The expression levels of TLR2,Interleukin-1 receptor-associated kinase(IRAK)and NF-κB mRNAs in the ischemic penumbra region of brain tissue were detected by real-time fluorescence quantitative PCR.Results Following modeling,the neurological deficit scores were significantly increased from the 3 rd day on after CIRI(P<0.05),the expression levels of TLR2 mRNA on day 3,7,14 and 28,and IRAK mRNA on day 3 and 7,as well as NF-κB mRNA on day 3,7 and 14 were significantly up-regulated in the model group relevant to the blank control group(P<0.05).After EA intervention,the neurological deficit scores were significantly decreased in the EA group on day 3,7 and 28 and in the EA+PDTC group on day 3,7,14 and 28 in comparison with those of the model group(P<0.05).In addition,the expression levels of TLR2 mRNA and NF-κB mRNA on day3,7 and 14 in the EA group,and on day 3,7,14 and 28 in the EA+PDTC group,IRAK mRNA on day 3 in the EA and EA+PDTC group were significantly down-regulated(P
作者 刘霜月 张玉莲 许潇莹 艾双春 LIU Shuang-yue;ZHANG Yu-lian;XU Xiao-ying;AI Shuang-chun(Health and Rehabilitation College,Chengdu Universityof Traditional Chinese Medicine,Chengdu610075,China;Department of Rehabilitation,Mianyang City Hospital of Traditional Chinese Medicine,Mianyang621000,Sichuan Province)
出处 《针刺研究》 CAS CSCD 北大核心 2019年第4期242-247,共6页 Acupuncture Research
基金 四川省绵阳市科技局项目基金(No.2015yy037) 四川省中医药管理局科研项目(No.2018LC022)
关键词 电针 脑缺血再灌注损伤 TLR2/NF-κB信号通路 白细胞介素-1受体相关激酶 Electroacupuncture Cerebral ischemia/reperfusion injury TLR2/NF-κB signaling Interleukin-1 receptor-associated kinase
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