Parkinson’s disease (PD) is one of most common neurodegenerative diseases. Environmental stressors such as oxidative stress (OS), calcium ion influx, apoptosis, and inflammation mechanisms are linked to activated microglia in patients with PD. The OS-dependent activated transient receptor potential melastatin 2 (TRPM2) channel is modulated in several neurons by glutathione (GSH). However, the cellular and molecular effects of GSH alteration on TRPM2 activation, OS, apoptosis, and inflammation in the microglia remain elusive. The microglia of TRPM2 wild-type (TRPM2-WT) and knockout (TRPM2-KO) mice were divided into control, PD model (MPP), l-buthionine sulfoximine (BSO), MPP + BSO and MPP + BSO + GSH groups. MPP-induced increases in apoptosis, death, OS, lipid peroxidation, PARP1, caspase-3 and caspase-9, inflammatory cytokines (IL-1β, TNF-α, IL-6), and intracellular free Zn²⁺ and Ca²⁺ levels in the microglia of TRPM2-WT mice were further increased by the BSO treatment, although they were diminished by the GSH treatment. Their levels were further reduced by PARP1 inhibitors (PJ34 and DPQ) and TRPM2 blockers (ACA and 2-APB). However, the effects of MPP and BSO were not observed in the microglia of TRPM2-KO mice. Taken together, our data demonstrate that maintaining GSH homeostasis is not only important for quenching OS in the microglia of patients with PD but also equally critical to modulating TRPM2, thus suppressing inflammatory responses elicited by environmental stressors.

帕金森病（PD）是最常见的神经退行性疾病之一。氧化应激 (OS)、钙离子流入、细胞凋亡和炎症机制等环境压力源与 PD 患者的活化小胶质细胞有关。谷胱甘肽 (GSH) 在几个神经元中调节 OS 依赖的激活瞬时受体电位 melastatin 2 (TRPM2) 通道。然而，GSH 改变对小胶质细胞中 TRPM2 激活、OS、细胞凋亡和炎症的细胞和分子影响仍然难以捉摸。TRPM2野生型（TRPM2-WT）和敲除（TRPM2-KO）小鼠的小胶质细胞分为对照、PD模型（MPP）、l-丁硫氨酸亚砜亚胺 (BSO)、MPP + BSO 和 MPP + BSO + GSH 基团。MPP 诱导的细胞凋亡、死亡、OS、脂质过氧化、PARP1、caspase-3 和 caspase-9、炎性细胞因子（IL-1β、TNF-α、IL-6）和细胞内游离 Zn ²⁺和 Ca ^{2+ 增加}BSO 处理进一步增加了 TRPM2-WT 小鼠小胶质细胞中的水平，尽管它们被 GSH 处理降低了。PARP1 抑制剂（PJ34 和 DPQ）和 TRPM2 阻滞剂（ACA 和 2-APB）进一步降低了它们的水平。然而，在 TRPM2-KO 小鼠的小胶质细胞中未观察到 MPP 和 BSO 的作用。总之，我们的数据表明，维持 GSH 体内平衡不仅对 PD 患者小胶质细胞中 OS 的淬灭很重要，而且对调节 TRPM2 也同样重要，从而抑制由环境压力源引起的炎症反应。