基于PI3K/Akt信号转导通路研究电针促颅脑损伤康复机制

Traumatic brain injury (TBI) is a large burden of family and society. The key of treatment TBI is to prevent cell apoptosis of cerebral neurons, and promote the rehabilitation of brain function. Clinical efficacy of Electroacupuncture for treating TBI is reliable, but the mechanism remains unclear. Previous research of our team have mastered the technology of TBI model preparation, and find that Electroacupuncture can adjust some of the factors that affect neuronal apoptosis. PI3K/Akt signal transduction pathway plays an important role in the regulation of the cerebral neurons apoptosis. There is no study on mechanisms of treatment about acupuncture on TBI from the PI3K/Akt signal transduction pathway at present throughout investigation of literature. We believe that " Electroacupuncture regulates program of neuronal apoptosis and promotes recovery after TBI via PI3K/Akt signal transduction pathway " is a scientific hypothesis. TBI model of rats were used as the research object, selecting "Baihui, Shuigou, Neiguan and Zusanli" as the acupoints of acupuncture therapy, Using electron microscopy and modern biotechnology of RNA interference, molecular biology etc. observe the regulating effects of Electroacupuncture on protein of downstream of PI3K/Akt signal transduction pathway and itself as well as genes miRNA-711, miRNA-21 that effect of PI3K/Akt from different levels and at different times. It is expected to elucidate the mechanism of Electroacupuncture for promoting rehabilitation of TBI, provide scientific experimental basis for extensive clinical application and studies of the treatment of Electroacupuncture on TBI.

颅脑损伤（TBI）给家庭和社会带来沉重负担,治疗的关键是阻止脑神经细胞凋亡，促使脑神经功能康复,电针治疗临床疗效确切,但机制不明。团队前期研究掌握了TBI模型制备技术，发现电针可调节影响脑神经元凋亡的一些因素。PI3K/Akt信号通路在细胞凋亡调控中起重要作用，经查文献，目前尚无从本通路研究电针治疗TBI的机制。本课题以“电针可通过PI3K/Akt信号转导通路调控TBI后脑细胞的凋亡程序，促TBI康复”为科学假说。以大鼠TBI模型为研究对象，采用“百会、水沟、内关、足三里”穴电针治疗，利用电子显微镜、基因干扰、分子生物学等现代检测技术，从不同层次和不同时间观察电针对TBI大鼠PI3K/Akt信号转导通路蛋白及其下游蛋白和影响PI3K/Akt相关基因miRNA-711、miRNA-21的调节作用。有望阐明电针促TBI康复的作用机制，为临床广泛应用和研究电针治疗TBI提供科学实验依据。

颅脑损伤（TBI）给家庭和社会带来沉重负担,治疗的关键是抑制脑神经细胞凋亡，促使脑神经功能康复,电针对TBI的治疗临床疗效确切,但机制不明。本课题以“电针可通过PI3K/Akt信号转导通路调控TBI后脑细胞的凋亡程序，促TBI康复”为科学假说。以大鼠TBI模型为研究对象，用形态学、分子生物学等现代检测技术，通过一系列实验，从不同层次和不同角度观察了电针对TBI大鼠PI3K/Akt信号转导通路关键蛋白及其下游神经元凋亡相关蛋白的调节作用。研究发现：（1）电针能有效改善TBI大鼠神经功能、平衡功能、行走功能、大鼠右侧前后肢肢体回缩力，减轻损伤脑组织出血、水肿、炎症，降低血清中NSE的浓度，抑制脑细胞凋亡，促进大脑功能的恢复。（2）电针能减少TBI大鼠脑组织中与炎症、细胞凋亡有关的TNF-α、Caspase-3、ERK蛋白及mRNA的表达量，增加与细胞存活、增值分化有关的AKT蛋白及mRNA的表达量，且电针介入治疗的时间越早，效果越好。（3）电针能明显抑制引起颅脑损伤大鼠脑水肿蛋白MMP-9及mRNA的表达量，增加消除脑细胞水肿、减轻炎症，并与细胞存活有关的AQP-4、TIMP-1蛋白及其mRNA的表达量，实验结果显示早期电针介入对脑水肿及细胞凋亡的预防效果更显著。（4）电针干预可下调TBI大鼠损伤脑组织中促凋亡蛋白Bad、bak、bax的表达，上调抗凋亡蛋白Bcl-2、NF-kB、bcl-xl的表达，从而抑制脑神经细胞的凋亡。（5）电针干预可上调TBI大鼠损伤脑组织中PI3K/Akt信号转导通路关键蛋白PI3K、PDK1、AKT、p-AKT及其mRNA的表达，且该效应受抑制剂LY294002的影响。（6）电针干预对TBI大鼠行为学功能和病理形态学的改善，以及对TBI大鼠的治疗效应与PI3K/AKT信号通路相关。

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