电针对血管性痴呆大鼠海马区c-Jun氨基末端激酶信号通路的影响  

Electroacupuncture improved learning-memory ability by reducing hippocampal apoptosis and suppressing JNK signaling in rats with vascular dementia

作　　者：郭菲 张素钊 陈世雨 张闯[3] 张晓琪 高飞 武泽惠 于文涛 梁玉磊 张会珍 GUO Fei;ZHANG Su-zhao;CHEN Shi-yu;ZHANG Chuang;ZHANG Xiao-qi;GAO Fei;WU Ze-hui;YU Wen-tao;LIANG Yu-lei;ZHANG Hui-zhen(College of Acupuncture and Moxibustion,Hebei University of Chinese Medicine,Shijiazhuang 050200,China;Department of Acupuncture and Moxibustion,Affiliated Hospital of Hebei University of Chinese Medicine,Shijiazhuang 050011;Research Center of Hebei University of Chinese Medicine,Shijiazhuang 050091)

机构地区：[1]河北中医学院针灸推拿学院,石家庄050200 [2]河北中医学院附属医院针灸科,石家庄050011 [3]河北中医学院科研中心,石家庄050091

出　　处：《针刺研究》2020年第1期21-26,共6页Acupuncture Research

基　　金：河北省高等学校科学技术研究重点项目(No.ZD2018017);河北省自然科学基金面上项目(No.H2013206245);河北省中医药管理局科技支撑项目(No.2011006、2013002)

摘　　要：目的:观察电针干预对血管性痴呆(VD)大鼠海马组织c-Jun氨基末端激酶(JNK)信号通路相关蛋白表达的影响,探讨电针治疗VD的作用机制。方法:雄性SD大鼠随机分为假手术组、模型组、电针组,每组10只。采用反复阻断双侧颈总动脉法制备VD大鼠模型。电针组电针"大椎""百会"及双侧"后三里""膈俞"穴,10min/次,1次/d,连续治疗14d。Morris水迷宫检测大鼠行为学变化,尼氏染色法观察海马神经元病理改变,原位末端转移酶标记(TUNEL)法检测海马神经元凋亡,Western blot法检测JNK、磷酸化JNK(p-JNK)、半胱氨酸蛋白酶-8(Caspase-8)、半胱氨酸蛋白酶-3(Caspase-3)蛋白表达。结果:与假手术组比较,模型组大鼠Morris水迷宫实验逃避潜伏期明显延长,穿越原平台次数明显减少(P<0.01),海马神经元损伤加重,存活神经元明显减少(P<0.01),凋亡神经元增多,细胞凋亡指数明显升高(P<0.01),海马组织JNK、p-JNK、Caspase-8、Caspase-3蛋白表达均明显升高(P<0.01)。与模型组比较,电针组大鼠Morris水迷宫逃避潜伏期明显缩短,穿越原平台次数明显增多(P<0.01),海马神经元损伤减轻,存活神经元明显增多(P<0.01),凋亡神经元减少,细胞凋亡指数明显降低(P<0.01),海马组织JNK、p-JNK、Caspase-8、Caspase-3表达均显著降低(P<0.01)。结论:电针可提高VD大鼠学习记忆能力,其作用机制可能与电针调控JNK信号通路相关蛋白表达,抑制神经元凋亡有关。Objective To observe the effect of electroacupuncture(EA)stimulation on the expression of c-Jun terminal kinase(JNK)signaling pathway-related proteins in the hippocampus of vascular dementia(VD)rats,so as to explore its mechanisms underlying improvement of VD.Methods Male Sprague-Dawley rats were randomly divided into sham operation,model and EA groups(n=10 rats per group).The VD model was prepared by repeated occlusion of the bilateral common carotid arteries for10 min and reperfusion for 10 min(3 times in total).The rats in the EA group received EA(2 Hz,2 mA)at "Dazhui"(GV14),"Baihui"(GV20),and bilateral"Housanli"(ST36),"Geshu"(BL17)for 10 min,once daily for 14 days.The learning-memory ability was detected by Morris water maze tests,the distribution of hippocampal neurons detected by Nissl staining,and the apoptosis of hippocampal neurons detected by using TdT-mediated dUTP nick-end labeling(TUNEL)method.The expressions of JNK,phosphorylated JNK(p-JNK),cysteine-containing aspartate-specific proteases-8(Caspase-8)and Caspase-3 proteins were detected by Western blot.Results After modeling and compared with the sham operation group,the escape latency was significantly prolonged(P<0.01)and the number of safe-platform quadrant crossing obviously decreased(P<0.01),suggesting a reduction of learning-memory ability.The number of hippocampal neurons was considerably reduced(P<0.01),and that of hippocampal apoptotic neurons remarkably increased in the model group(P<0.01).Whereas,the expression levels of hippocampal apoptosis-related proteins as JNK,p-JNK,Caspase-8 and Caspase-3,as well as the apoptotic index were significantly up-regulated(P<0.01).Following EA intervention,the learning-memory ability was apparently improved(P<0.01),and the number of hippocampal neurons was considerably increased(P<0.01),the hippocampal apoptotic cell number,apoptosis index and the expression levels of JNK,p-JNK,Caspase-8 and Caspase-3 were significantly down-regulated(P<0.01).Conclusion EA intervention can improve the learning-memory abi

关 键 词：血管性痴呆 电针 缺血再灌注 学习记忆能力 海马 c-Jun氨基末端激酶信号通路 

分 类 号：R245.97[医药卫生—针灸推拿学]