CX3CR1在嗅鞘细胞协同TGF-β1抑制炎症反应修复视神经损伤的作用及机制研究

Microglia plays an important role in the inflammatory response after optic nerve injury. The polarization of the microglia is the reason that they have neurotoxicity and neuroprotection. The study shows that transplanted olfactory ensheathing cells (OECs) into injured central nervous system can change the polarization state of microglia and reduce its neurotoxicity. However, it is still remains in understanding of the molecular mechanisms, which OECs how to induce microglia to M2 polarization state. Our previous study found it is closely related to CX3CL1-CX3CR1 signal. In the present project, we plan to (1) establish OECs and microglia cells co-culture system in vitro, and investigate OECs how to affect polarization state of microglia , (2) further elucidate that CX3CL1-CX3CR1 signal how to affect microglia transformed to M2 polarization state. (3)Proven the effect transplanted OECs into injured optic nerve on microglia polarization state. And combined application of OECs and transforming growth factor beta 1 (TGF-β1), upregulate expression of CX3CR1 on microglia and promote the activation of microglia transform to M2 polarization state. We hope that the present project can provide a new strategy to repair optic nerve injury in human patients, and exploration of the mechanisms underlying the effects of OEC on polarization state of microglia. It can provide theoretical basis for transplanted OECs treatment injuryed optic nerve.

以小胶质细胞为主的免疫炎症反应是视神经损伤后修复的瓶颈，如何降低其毒性作用，发挥其神经保护作用是研究热点。研究发现嗅鞘细胞（OECs）可以改变小胶质细胞的极化状态，而降低其神经毒性作用。然而机制尚不清楚。我们前期研究发现，OECs对小胶质细胞的极化状态作用与CX3CL1-CX3CR1信号密切相关。本项目拟建立体外OECs与小胶质细胞共培养体系，研究OECs对小胶质细胞不同极化状态的作用，并进一步阐明CX3CL1-CX3CR1在OECs促小胶质细胞向M2状态转化的分子机制。探明移植的OECs对视神经损伤处小胶质细胞/巨噬细胞极化状态的作用，并联合应用OECs与转化因子TGF-β1，观察TGF-β1上调小胶质细胞CX3CR1表达及促进激活的小胶质细胞向M2状态转化的情况，检测减轻炎症反应的变化及改善损伤视神经内恶劣的中枢神经系统微环境、促进损伤轴突再生作用，最终与上丘重建形态和功能。

我们的研究发现嗅鞘细胞（OECs）可以改变小胶质细胞的极化状态，而降低其神经毒性作用。本项目建立了体外OECs与小胶质细胞共培养体系，研究了OECs对小胶质细胞不同极化状态的作用，并进一步阐明在OECs促小胶质细胞向M2状态转化的可能分子机制。对视神经损伤处小胶质细胞/巨噬细胞极化状态的作用，并联合应用OECs与转化因子TGF-β1，观察了TGF-β1上调小胶质细胞CX3CR1表达及促进激活的小胶质细胞向M2状态转化的情况，检测减轻炎症反应的变化及改善损伤视神经内恶劣的中枢神经系统微环境、促进损伤轴突再生作用。..