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硒酸盐有益于帕金森病胚胎干细胞治疗。

Selenite benefits embryonic stem cells therapy in Parkinson's disease.

机构信息

Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

出版信息

Curr Mol Med. 2012 Sep;12(8):1005-14. doi: 10.2174/156652412802480880.

Abstract

Embryonic stem cells (ESC) transplantation is a potential therapeutic approach for Parkinson's disease (PD). However, one of the main challenges to this therapy is the post-transplantation survival of dopaminergic (DA) neurons. In this study, mouse ESC were differentiated into DA neurons by a modified serum free protocol. These ESC-derived neurons were then transplanted into striatum of 6-OHDA lesioned rat. The viability of grafted DA neurons was decreased, accompanied by activated microglia and high levels of proinflammatory factors, such as TNF-α and iNOS, in the graft niche. This suggested that the local neuroinflammation might be involved in the reduced cells viability. Selenite, the source of essential micronutrient selenium, could inhibit NF-κB p65 nuclear translocation and subsequently reduce iNOS, COX-2 and TNF-α expression in LPS-treated BV2 cells in a dose dependant manner. Before the transplantation of ESC-derived DA neurons, 6-OHDA lesioned rats were intraperitoneally injected with selenite. The expression levels of TNF-α and iNOS were decreased by 30% and 50%, respectively, in selenite treated group. The survival of implanted DA neurons and the rotational behavior of transplanted rats were also remarkably improved by selenite treatment. To sum up, selenite might benefit ESCs transplantation therapy in PD through anti-inflammation effects.

摘要

胚胎干细胞(ESC)移植是治疗帕金森病(PD)的一种有潜力的治疗方法。然而,这种治疗方法的主要挑战之一是多巴胺能(DA)神经元的移植后存活。在这项研究中,通过改良的无血清方案将小鼠 ESC 分化为 DA 神经元。然后将这些 ESC 衍生的神经元移植到 6-OHDA 损伤的大鼠纹状体中。移植的 DA 神经元的活力降低,伴随着移植部位激活的小胶质细胞和高水平的促炎因子,如 TNF-α 和 iNOS。这表明局部神经炎症可能参与了细胞活力的降低。亚硒酸钠是必需微量元素硒的来源,它可以抑制 NF-κB p65 的核转位,并随后以剂量依赖的方式降低 LPS 处理的 BV2 细胞中 iNOS、COX-2 和 TNF-α 的表达。在移植 ESC 衍生的 DA 神经元之前,用亚硒酸钠对 6-OHDA 损伤的大鼠进行腹腔注射。亚硒酸钠处理组 TNF-α 和 iNOS 的表达水平分别降低了 30%和 50%。植入的 DA 神经元的存活和移植大鼠的旋转行为也因亚硒酸钠治疗而显著改善。总之,亚硒酸钠可能通过抗炎作用有益于 PD 中的 ESC 移植治疗。

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