Gao Shao-Jie, Li Dan-Yang, Liu Dai-Qiang, Sun Jia, Zhang Long-Qing, Wu Jia-Yi, Song Fan-He, Zhou Ya-Qun, Mei Wei
66375Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology.
Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China66375Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology.
Mol Pain. 2022 Sep 6;18:17448069221124920. doi: 10.1177/17448069221124920.
Osteoarthritis (OA), a chronic degenerative disease, leads to pain and loss of function. Existing treatments for OA pain have limited efficacy and show significant side effects. Dimethyl fumarate, a robust nuclear factor erythroid 2-related factor 2 (Nrf2) activator, could alleviate pain behaviors in chronic pain. This study aims to investigate the role of dimethyl fumarate in a rat model of OA and its underlying mechanisms.
We used von Frey filaments to assess the mechanical allodynia. Weight-bearing apparatus was employed to assess the hindlimb weight distribution. Western blot was employed to investigate the protein expressions of mitochondrial biogenesis markers. RT-qPCR was employed to examine the copy number of mitochondrial DNA (mtDNA).
Dimethyl fumarate upregulated mechanical paw withdrawal threshold (MIA + Vehicle, 1.6 ± 0.13g [mean ± SEM]; MIA + DMF, 10.5 ± 0.96g; P ＜ 0.0001). Hindlimb weight distribution was alao upregulated by dimethyl fumarate (MIA + Vehicle, 38.17 ± 0.72g; MIA + DMF, 43.59 ± 1.01g; P ＜ 0.01). Besides, activation of Nrf2 remarkably upregulated the protein levels of PGC-1α (MIA + Vehicle, 0.69 ± 0.07; MIA + DMF, 1.08 ± 0.09; P = 0.0037), NRF1 (MIA + Vehicle, 0.69 ± 0.04; MIA + DMF, 1.00 ± 0.11; P = 0.0114), TFAM (MIA + Vehicle, 0.62 ± 0.11; MIA + DMF, 1.02 ± 0.12; P = 0.0147), and the copy number of mtDNA(MIA + Vehicle, 0.52 ± 0.05; MIA + DMF, 3.81 ± 0.21; P ＜ 0.0001) Conclusions: Taken together, these results show that dimethyl fumarate alleviated pain-related behaviors in a rat model of OA through activation of Nrf2-induced mitochondrial biogenesis.
骨关节炎（OA）是一种慢性退行性疾病，会导致疼痛和功能丧失。现有的OA疼痛治疗方法疗效有限且有明显副作用。富马酸二甲酯是一种强大的核因子红细胞2相关因子2（Nrf2）激活剂，可减轻慢性疼痛中的疼痛行为。本研究旨在探讨富马酸二甲酯在OA大鼠模型中的作用及其潜在机制。
我们使用von Frey细丝评估机械性异常性疼痛。使用负重装置评估后肢重量分布。采用蛋白质印迹法研究线粒体生物发生标志物的蛋白表达。采用逆转录定量聚合酶链反应（RT-qPCR）检测线粒体DNA（mtDNA）的拷贝数。
富马酸二甲酯上调了机械性缩爪阈值（MIA + 赋形剂组，1.6±0.13g [平均值±标准误]；MIA + 富马酸二甲酯组，10.5±0.96g；P＜0.0001）。富马酸二甲酯也上调了后肢重量分布（MIA + 赋形剂组，38.17±0.72g；MIA + 富马酸二甲酯组，43.59±1.01g；P＜0.01）。此外，Nrf2的激活显著上调了PGC-1α的蛋白水平（MIA + 赋形剂组，0.69±0.07；MIA + 富马酸二甲酯组，1.08±0.09；P = 0.0037）、NRF1（MIA + 赋形剂组，0.69±0.04；MIA + 富马酸二甲酯组，1.00±0.11；P = 0.0114）、线粒体转录因子A（TFAM）（MIA + 赋形剂组，0.62±0.11；MIA + 富马酸二甲酯组，1.02±0.12；P = 0.0147）以及mtDNA的拷贝数（MIA + 赋形剂组，0.52±0.05；MIA + 富马酸二甲酯组，3.81±0.21；P＜0.0001）。结论：综上所述，这些结果表明富马酸二甲酯通过激活Nrf2诱导的线粒体生物发生减轻了OA大鼠模型中与疼痛相关的行为。
