Department of Anesthesiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), China.
Department of Pain, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), China.
Int J Biochem Cell Biol. 2024 Nov;176:106675. doi: 10.1016/j.biocel.2024.106675. Epub 2024 Oct 11.
Given the unclear, complex pathogenesis of neuropathic pain and the potential of paeoniflorin in relieving neuropathic pain, this study aimed to further clarify the therapeutic effect of paeoniflorin on neuropathic pain and to preliminarily explore the possible protective mechanisms of paeoniflorin. Chronic constrictive injury-induced Sprague Dawley rats and lipopolysaccharide-induced BV-2 cells were used for in vivo and in vitro experiments, respectively. The exosome uptake assay of mouse astrocytes (PKH-67 fluorescent labeling) and the mechanical nociceptive assay (the von Frey fibrous filaments) were performed. The effects of paeoniflorin and its downstream mechanisms on microglial and astrocyte activation, inflammation-associated proteins and exosome marker were determined. Paeoniflorin alleviated mechanical abnormal pain, decreased levels of ionized calcium binding adapter molecule-1 (Iba-1), glial fibrillary acidic protein, Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1, inflammatory factor) and High Mobility Group Box 1 (HMGB1, inflammation-related protein), and inhibited neuronal apoptosis in chronic constrictive injury rats or lipopolysaccharide-induced BV-2 cells. However, these effects were offset by HSP90AA1 overexpression in lipopolysaccharide-induced BV-2 cells. Exosomes of BV-2 cells could be absorbed by mouse astrocytes. In addition, HSP90AA1 overexpression reversed the effects of paeoniflorin on HMGB1 expression and inflammatory factors and proteins in mouse astrocytes co-cultured with exosome. Collectively, paeoniflorin alleviates neuropathic pain and inhibits inflammatory responses in chronic constrictive injury by modulating microglia-astrocyte crosstalk through HSP90AA1/HMGB1 pathways, which further evidences the potential of paeoniflorin in the treatment of neuropathic pain.
鉴于神经病理性疼痛的发病机制不明确且复杂，以及芍药苷缓解神经病理性疼痛的潜力，本研究旨在进一步阐明芍药苷治疗神经病理性疼痛的疗效，并初步探讨芍药苷的可能保护机制。分别使用慢性缩窄性损伤诱导的 Sprague Dawley 大鼠和脂多糖诱导的 BV-2 细胞进行体内和体外实验。对小鼠星形胶质细胞（PKH-67 荧光标记）的外体摄取实验和机械性痛觉测定（von Frey 纤维丝）进行了操作。测定了芍药苷及其下游机制对小胶质细胞和星形胶质细胞活化、炎症相关蛋白和外体标志物的影响。芍药苷缓解了机械性异常疼痛，降低了离子钙结合接头分子-1（Iba-1）、神经胶质纤维酸性蛋白、热休克蛋白 90α 家族成员 1（HSP90AA1，炎症因子）和高迁移率族蛋白 B1（HMGB1，炎症相关蛋白）的水平，并抑制了慢性缩窄性损伤大鼠或脂多糖诱导的 BV-2 细胞中的神经元凋亡。然而，在脂多糖诱导的 BV-2 细胞中过表达 HSP90AA1 后，这些作用被抵消。BV-2 细胞的外体可以被小鼠星形胶质细胞吸收。此外，HSP90AA1 过表达逆转了芍药苷对与外体共培养的小鼠星形胶质细胞中 HMGB1 表达和炎症因子及蛋白的影响。综上所述，芍药苷通过 HSP90AA1/HMGB1 通路调节小胶质细胞-星形胶质细胞串扰，减轻慢性缩窄性损伤引起的神经病理性疼痛并抑制炎症反应，进一步证明了芍药苷在治疗神经病理性疼痛方面的潜力。
