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近来的研究表明,神经炎症在帕金森病(Parkinson’sdisease,PD)的发病过程中起着重要的作用,因此通过抑制神经炎症而保护黑质多巴胺能神经元可能是一种具有潜力的治疗策略。本研究组前期的临床试验表明,灵芝(Ganoderma lucidum,GL)具有潜在的神经保护作用,可能通过抗炎及免疫调节机制发挥其保护作用。本研究在神经元-小胶质细胞共培养的模型中观察了GL的神经保护作用,并探讨其可能的保护机制。小胶质细胞单独或与MES23.5多巴胺能神经细胞共培养,脂多糖(lipopolysaccharide,LPS,0.25μg/mL)孵育24h作为阳性对照,试验组分别加入GL提取物(50~400μg/mL)和/或MPP+处理的MES23.5细胞膜碎片(150μg/mL);检测小胶质细胞激活情况及其产生的有害因子和MES23.5细胞[3H]DA摄取能力。结果显示,LPS或MPP+损伤的MES23.5膜碎片均可激活小胶质细胞。同时,GL提取物可以显著降低小胶质细胞源性炎症因子和细胞毒性因子(NO、TNF-α、L-1β)的产生,并呈一定的浓度依赖性;并同样可以下调TNF-α和L-1β mRNA水平的表达。此外,GL还可明显对抗由小胶质细胞激活和MPP+介导的多巴胺能神经细胞[3H]DA摄取抑制。以上结果提示,GL主要通过抑制小胶质细胞激活,减少其神经毒性因子的释放而保护多巴胺能神经细胞。GL可能成为治疗PD的潜在药物。
Recent studies have shown that neuroinflammation plays an important role in the pathogenesis of Parkinson’s disease (PD). Therefore, protecting the substantia nigra dopaminergic neurons by inhibiting neuroinflammation may be a potential therapeutic strategy . Our previous clinical trials showed that Ganoderma lucidum (GL) has potential neuroprotective effect and may exert its protective effects through anti-inflammatory and immunomodulatory mechanisms. In this study, the neuroprotective effect of GL was observed in a model of neuron-microglial co-culture and its possible protective mechanism was explored. Microglia alone or in co-culture with MES23.5 dopaminergic neurons, and lipopolysaccharide (LPS, 0.25μg / mL) for 24 hours as positive control. GL extract (50-400μg / mL) and / MPS23.5 membrane fragments treated with MPP + (150μg / mL). The microglial activation and its harmful factors and the [3H] DA uptake ability of MES23.5 cells were detected. The results showed that both MPS23.5 membrane fragments damaged by LPS or MPP + could activate microglial cells. At the same time, GL extract can significantly reduce the production of microglial-derived inflammatory cytokines and cytokines (NO, TNF-α, L-1β) in a concentration-dependent manner; L-1β mRNA expression. In addition, GL also significantly antagonizes the uptake inhibition of [3H] DA by microglial activation and MPP + -mediated dopaminergic neurons. The above results suggest that GL protects dopaminergic neurons mainly through inhibiting microglial activation and decreasing the release of neurotoxic factors. GL may be a potential drug for the treatment of PD.