成体细胞通过去分化、转分化及重编程获得分化潜能是再生医学研究热点之一。在神经再生过程中，“华勒氏变性”及“雪旺细胞去分化”都是其至关重要的环节。IL-1β是华勒氏变性早期的重要参与因素之一，具有促进神经元的存活，神经突生长等多种生物活性，而IL-1β对雪旺细胞去分化作用却鲜有报道。在前期实验研究中，我们通过大鼠坐骨神经华勒氏变性体外模型，发现华勒氏变性早期IL-1β具有通过c-Jun/AP-1通路促进雪旺细胞去分化的作用（详见预实验研究）。本课题将构建坐骨神经华勒氏变性体外模型以及坐骨神经损动物模型，进一步研究IL-1β在周围神经华勒氏变性早期对雪旺细胞去分化的影响，阐明IL-1β对雪旺细胞去分化关键通路c-Jun/AP-1的作用，并探索调控机制，为解决神经损伤修复再生过程中“新生组织的细胞来源”问题提供新的理论依据。

The ultimate goal of regenerative medicine research is to enable replacement of lost or damaged tissues or organs. Regeneration can potentially be accomplished using the processes of de-differentiation, trans-differentiation or reprogramming. Humans have a limited capacity to regenerate tissues or organs, including liver and the peripheral nervous system (PNS). In some cases, the process of regeneration involves de-differentiation of mature cells. De-differentiation is a mechanism in which terminally-differentiated cells revert to a less-differentiated stage within the same lineage and allows cells to proliferate before re-differentiating, leading to the replacement of lost cells..Schwann cells (SCs), myelinated glial cells of the PNS, de-differentiate and revert to an immature phenotype in Wallerian degeneration (WD) following nerve injury and, by doing so, can actively promote nerve repair and functional recovery. Following de-differentiation, SCs contribute to macrophage-mediated myelin removal and re-enter the cell cycle, proliferate, and then form bands of Büngner, which support and direct outgrowing axons to sites of innervation. Moreover, these cells express and secrete axonal growth promoting factors, then re-differentiate and myelinate regenerated axons, which eventually leads to substantial functional recovery. This sequence emphasizes the central function of SC de-differentiation in PNS regeneration..WD can be considered an innate-immune response of the PNS to traumatic nerve injury. PNS injury induces immune and non-immune cells to produce cytokines and develop an efficient cytokine network during WD. Before macrophage recruitment, injured PNS product IL-1β and other inflammatory cytokines. IL-1β induces macrophage recruitment and then aids myelin clearance, which facilitates axonal outgrowth. In addition to a role in immune responses, IL-1β direct and indirect promotes neuronal survival. Moreover IL-1β promotes SCs proliferation and increases nerve growth factor synthesis by SCs. Previous in vivo studies indicate that these effects of IL-1β on WD are supposed to provide sciatic nerve regeneration. These suggest that IL-1β plays an important role during PNS regeneration. On top of that, IL-1β can influence de-differentiation in some types of terminally differentiated cells. For example, IL-1β induces chondrocyte de-differentiation. However, whether IL-1β promotes SCs de-differentiation during WD remains to be clearly determined. To demonstrate hypothesis that, in addition to a role in immune responses, IL-1β participates in SC de-differentiation, proliferation and apoptosis, and promotes regeneration of PNS, we used a rodent in vitro & vivo model investigate effect and mechanism of IL-1β on schwann cells dedifferentiation at early phase of Wallerian Degeneration.