领导这一研究的是健康研究所张雁云教授，其早年毕业于苏州医学院，曾在日本东京大学医学部进修学习，目前任中国科学院上海生命科学研究院/上海交通大学医学院健康科学研究所研究员，研究组长。
脂代谢调节的紊乱会导致多种**的发生，但是其对神经再生修复和神经**功能的影响目前还尚不清楚。内固醇受体辅激活因子(SRC-3)是机体脂代谢调节中重要转录因子，研究人员发现，SRC3基因敲除小鼠较野生型小鼠瘦小，且其脂代谢水平较高。
研究人员利用SRC-3基因敲除小鼠构建实验性自身**性脑脊髓炎(EAE)模型，发现基因敲除小鼠表现出对EAE诱导的耐受。其原因是SRC3基因敲除促进了炎症条件下**神经系统(CNS)中小胶质细胞处于一种非经典的激活状态，这些非经典激活的小胶质细胞通过上调**症细胞因子IL-10的表达来对抗EAE诱导引起的CNS炎症，并促进了CNS少突胶质细胞诱导的髓鞘再生。
进一步分析相关的机制，发现这种非经典激活的小胶质细胞是由于SRC3基因敲除诱导了炎症条件下CNS中PPAR-β的升高引起的，也调节了神经干细胞的活化、增殖和分化。在此研究中，**揭示了CNS小胶质细胞的非经典激活形式及**症效应及其相关分子机制，也发现了调节影响神经干细胞活化、增殖分化及再生修复病理损伤的重要代谢分子信号途径，为神经干****修复损伤提供了新的思路。另外一篇文章中，研究人员发现，18β甘草次酸通过抑制趋化因子巨噬细胞炎症蛋白-1a（MIP-1a）而缓解了爆发性肝炎及急性肝衰竭的发生。在研究应用的Propionibacteriumacnes诱导的急性肝炎**模型中，18β甘草次酸抑制了MIP-1a的表达，减少了由此引起的外周血CD11c+B220-树突状细胞的前体细胞的募集及其向肝脏的迁移，进而降低了对肝脏浸润的CD4+T细胞的激活和增殖，并导致炎症性细胞因子如IFN-g和TNF-a等产生的减少，达到了减轻肝脏炎症损伤的效应。深入的机制探讨研究发现，18β甘草次酸是通过降低肝脏Kupffer细胞MyD88的表达，阻止其下游信号通路NF-kB的活化，使Propionibacteriumacnes对Kupffer细胞的激活被抑制，MIP-1a产生减少。
此项研究不仅揭示了中药单体18β甘草次酸在急性肝炎模型中的**症和保护肝脏作用的分子机制，也发现了对肝脏急性炎症及肝衰竭的可调控靶点，为进一步筛选相关**和研究靶向**新策略提供了理论基础和实验依据。原文检索：
Genetic ablation of steroid receptor coactivator-3 promotesPPAR--mediated alternative activation of microglia in experimentalautoimmune encephalomyelitisSteroid receptor coactivator-3 (SRC-3) has been demonstrated toregulate lipid metabolism by inhibiting adipocyte differentiation.In this study, the potential role of SRC-3 in experimentalautoimmune encephalomyelitis (EAE), which characterized byinflammatory demyelination in central nervous system (CNS), wasexamined by analyzing disease progression in SRC-3-deficient(SRC-3-/-) mice. We found that SRC-3 deficiency significantlyattenuated the disease severity of EAE along with decreasedinflammatory infiltration and demyelination. However, these effectsare not caused by inhibition of peripheral T cell response, but byupregulated expression of peroxisome proliferator-activatedreceptor (PPAR)- in CNS, which induced an alternative activationstate of microglia in SRC-3-/- mice. These alternatively activatedmicroglia inhibited CNS inflammation through inhibition ofproinflammatory cytokines and chemokines, such as TNF-, IFN-, CCL2,CCL3, CCL5, and CXCL10, as well as upregulation ofanti-inflammatory cytokine IL-10 and opsonins, such as C1qa andC1qb. Moreover, microglia alternative activation promoted myelinregeneration through increased accumulation of oligodendrocyteprecursors in white matter and elevated expression of myelin genesin the spinal cords of SRC-3-/- mice. Our results build up a linkbetween lipid metabolic regulation and immune functions, and themodulation of the expression of SRC-3 or PPAR- may hopefully hastherapeutic modality in MS and possibly other neurodegenerativediseases. ? 2010 Wiley-Liss, Inc.