PI3Kγ/Akt通路在骨癌痛脊髓中枢敏感化中的作用研究

项目名称： PI3Kγ/Akt通路在骨癌痛脊髓中枢敏感化中的作用研究

项目编号： No.81460176

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 许冰

作者单位： 广西中医药大学

项目金额： 47万元

中文摘要： 骨癌痛是癌症骨转移和原发性骨肉瘤最常见的并发症。因其确切的发病机制未明，缺乏有效的治疗手段。脊髓中枢敏感化是骨癌痛的重要发病环节。研究发现配体门控通道、受体酪氨酸蛋白激酶（RTKs）或G蛋白偶联受体（GPCR）等多条路径通过PI3K/Akt通路参与介导各种炎性痛与神经病理性痛引起的脊髓中枢敏感化。同时发现GPCR、RTKs及配体门控通道同时参与介导骨癌痛的发生发展，且与PI3Kγ/Akt密切相关。另外骨癌痛导致脊髓胶质细胞活化与增殖，而胶质细胞与神经元存在密切联系，且PI3K/Akt可参与细胞的增殖与分化。因此我们提出假说：PI3Kγ/Akt直接作用脊髓背角神经元引起神经元敏感化，和（或）通过介导脊髓胶质细胞的活化与增殖，增强胶质细胞与神经元的功能联系从而引起脊髓中枢敏感化。本项目拟建立骨癌痛模型,运用行为学、组化、生化、电生理学和转基因技术验证这假说，为研发治疗骨癌痛药物提供理论依据。

中文关键词： 骨癌痛；磷脂酰肌醇-3-激酶；中枢敏感化；蛋白激酶B；脊髓背角

英文摘要： Bone cancer pain (BCP) is the most common complications in patients suffering from metastatic bone cancer or primary bone cancer. But the specific mechanisms underlying BCP remain elusive, and it is inadequately addressed by currently available treatment. Emerging lines of evidence indicate that spinal central sensitization is required for the development and maintenance of BCP. Ligand-gated ion channels,G protein-coupled receptors (GPCRs)and receptor tyrosine kinases (RTKs) play a key role in the spinal central sensitization induced by many kinds of inflammatory pain and neuropathic pain through PI3K/Akt pathway. Ligand-gated ion channels, GPCRs and RTKs mediate the development of BCP simultaneously, and there are crosstalk between these pathways and PI3Kγ/Akt pathways. Meanwhile,spinal glial cells were activated and proliferated under BCP condition, and PI3K/Akt pathway can promote cells proliferatin and differentiation.Also,glial cells communicate with neurons tightly.So we hypothesis that PI3Kγ/Akt directly induce neurol sensitization in spinal cord, and (or) through promoting the activation and proliferation of glial cells, which enhance the connection between glial cells and neurons.Our project will provide evidence to support this hypothesis by using behaviors, immunohistchemisty, molecular biology,electrophysiology and gene deficent technology in BCP rats/mouse, which will provide theory support for the development of drug treating BCP.

英文关键词： Bone cancer pain;PI3K;Central sensitization;Akt;Spinal dorsal horn