中文摘要
本研究在慢性神经痛 (CCI) 大鼠上，采用行为学、免疫细胞化学、定量PCR、电镜、差异蛋白质组学等技术，观察到重复电针"足三里-阳陵泉"具有累积性镇痛效应，并与动物的记忆能力有关。电针的累积镇痛效应与其1）上调海马CA3、CA1区、下丘脑室旁核(PVN)神经末梢突触素（SYN）的表达； 2）上调下丘脑PVN、海马CA3区钙调蛋白激酶（CaMKII）的免疫活性；3) 上调海马CA1和下丘脑PVN区的蛋白激酶A(PKA)的免疫活性；4)下调海马脑源性神经生长因子(BDNF)mRNA表达和上调下丘脑BDNFmRNA的表达；5）改善CCI及OVX+CCI引起的海马CA3区和下丘脑PVN神经元突触间隙、突触后致密层(PSD)厚度、突触活性带长度、突触界面曲率的减小，调节突触的可塑性紧密相关。海马、下丘脑组织中具有能量代谢、蛋白折叠及信号转导等功能的多种差异表达的蛋白质，细胞内与记忆相关的CaMKII介导的cAMP－PKA信号转导通路很可能参与了电针的累积效应。本研究深入揭示了重复电针产生累积性镇痛效应的生物学机制，为临床针刺治疗慢性痛提供了科学依据。
英文摘要
In sciatic nerve-ligature induced chronic constrictive injury (CCI) pain model (rats), and by using ethology, immunohistochemistry, real-time quantitative polymerase chain reaction(RT-PCR), electronic microscope, and differentially-expressed proteomics techniques, the present study observed that repeated electroacupuncture (EA) of "Zusanli"(ST36)-"Yanglingquan"(GB34) had a cumulative analgesic effect， and the effect was closely associated with the animals' memory. EA-induced cumulative analgesia was closely related its effects in 1) upregulating the expression of synaptophysin of the nerve endings of hippocampal CA3 and CA1 regions and hypothalamic paraventricular nucleus (PVN); 2) upregulating the immunoactivity of calcium/calmodulin-dependent protein kinase II (CaMKII) of hypothalamic PVN and hippocampal CA3; 3) upregulating the immunoactivity of hippocampal CA1 and hypothalamic PVN; 4) downregulating the expression of hippocampal brain-derived nerve growth factor (BDNF) mRNA and upregulating hypothalamic BDNF mRNA expression; 5) ameliorating changes of CCI and OVX+CCI induced reduction of the synaptic cleft, post-synaptic density thickness, length of synaptic active zone, and curvature of synaptic interface of neurons in hippocampal CA3 and hypothalamic PVN. Many differentially expressed proteins functioning
结题摘要
本研究在慢性神经痛 (CCI) 大鼠上，采用行为学、免疫细胞化学、定量PCR、电镜、差异蛋白质组学等技术，观察到重复电针"足三里-阳陵泉"具有累积性镇痛效应，并与动物的记忆能力有关。电针的累积镇痛效应与其1）上调海马CA3、CA1区、下丘脑室旁核(PVN)神经末梢突触素（SYN）的表达； 2）上调下丘脑PVN、海马CA3区钙调蛋白激酶（CaMKII）的免疫活性；3) 上调海马CA1和下丘脑PVN区的蛋白激酶A(PKA)的免疫活性；4)下调海马脑源性神经生长因子(BDNF)mRNA表达和上调下丘脑BDNFmRNA的表达；5）改善CCI及OVX+CCI引起的海马CA3区和下丘脑PVN神经元突触间隙、突触后致密层(PSD)厚度、突触活性带长度、突触界面曲率的减小，调节突触的可塑性紧密相关。海马、下丘脑组织中具有能量代谢、蛋白折叠及信号转导等功能的多种差异表达的蛋白质，细胞内与记忆相关的CaMKII介导的cAMP－PKA信号转导通路很可能参与了电针的累积效应。本研究深入揭示了重复电针产生累积性镇痛效应的生物学机制，为临床针刺治疗慢性痛提供了科学依据。