牛膝多肽对周围神经损伤中施万细胞的保护及作用研究

项目名称： 牛膝多肽对周围神经损伤中施万细胞的保护及作用研究

项目编号： No.81471259

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 袁颖

作者单位： 南通大学

项目金额： 70万元

中文摘要： 周围神经损伤后的反应分子ROS既可以诱导炎症产生，促进细胞凋亡，但也能激发神经的再生。如何既控制ROS产生，同时对炎症因子介导的细胞凋亡又有保护作用，成为神经损伤修复的研究热点。在自主研发的中药有效成分牛膝多肽（ABPP）对外周神经损伤后形态和功能保护的研究基础上，我们发现ABPP能有效防止腓总神经横断后神经元的丢失，诱导施万细胞ROS的产生，同时却对炎症因子TNF-α介导的细胞凋亡有保护作用，但机制尚不清楚。本课题拟建立ABPP保护TNF-α干预的损伤模型，阐明ABPP对TNF-α诱发的凋亡保护作用；体外模型揭示ABPP消减TNF-α引发施万细胞凋亡的分子机制，寻找ABPP保护损伤神经的作用细胞和分子靶点；明确ABPP对施万细胞ROS产生的信号机制以及功能；在体干预关键靶分子，阐明其对损伤神经的影响。通过ABPP对施万细胞ROS的产生和炎症保护机理研究，为中药有效成分的应用提供理论基础。

中文关键词： 牛膝多肽；周围神经；施万细胞；TNF-a；ROS

英文摘要： The production of ROS following peripheral nerve injury can induce inflammatory response, which results to the cellular apoptosis. At meantime, it is able to trigger the neural regeneration. So, studies on how to control the ROS production and how to protect the neural cells from apoptosis mediated by inflammatory cytokines become the spotlight in the repair of injured nerves. Our previous research found that the Traditional Chinese Medicine active ingredients, Achyranthes Bidentata Polypeptides (ABPP) had the protective effects on the morphology and function after peripheral nerve injury. ABPP could prevent the loss of neurons in the peroneal nerve transection effectively, and induced the ROS production of Schwann cell, as well as protected the cell against apoptosis in response to the TNF-α challenge, but the related mechanisms are not clear. For further address the questions above, we are going to establish the ABPP protective model against TNF-α intervention, in attempt to clarify the protective function of ABPP against the Schwann cell apoptosis mediated by TNF-α; we also try to reveal the molecular signaling as to ABPP attenuating the Schwann cell apoptosis induced by TNF-α, expecting to unveil the target cells and target molecules of ABPP action; we will take insight to the function and molecular mechanism of ABPP regarding to the induction of ROS production in the Schwann cell; at last, we are going to uncover the regenerative effects by intervention of key regulators in the injured nerves. With the researches of ABPP on inducing the ROS production of Schwann cell, and on protective effects on the apoptosis mediated by inflammation, we will provide the beneficial data for application of the Traditional Chinese Medicine active ingredients.

英文关键词： Achyranthes bidentata polypeptides;peripheral nerve;Schwann cell;TNF-a;ROS