化疗引起的周围神经病变（CIPN）是对化疗药物的严重不良反应，严重影响了化疗的疗效和患者的生活质量。尽管这种情况普遍存在，但缺乏有效的治疗方法。我们之前的研究发现臭氧能够缓解神经病理疼痛。损伤相关分子模式（DAMPs）或Toll样受体4（TLR4）或组织因子（TF）介导的神经炎症和微循环障碍是CIPN的主要原因。细胞因子信号抑制蛋白（SOCS）3是通过抑制TLR4抑制炎症的内源性负反馈调节因子。巯替脂（L-OHP）被用来建立小鼠的CIPN模型。通过观察ICR小鼠在机械压痛反应实验中足部退缩的发生率来评估痛觉反应。Western blot和免疫组化试验进行了细胞信号分析。培养了单核-巨噬细胞株RAW 264.7的小鼠白血病细胞用于研究臭氧治疗对巨噬细胞的影响。臭氧降低了血液和坐骨神经中的TF表达。它通过上调腺苷5'-单磷酸（AMP）激活的蛋白激酶（AMPK）-SOCS3轴来缓解CIPN并抑制TF表达。臭氧诱导SOCS3表达以抑制RAW 246.7细胞中的p38/TF信号。臭氧还预防了L-OHP引起的坐骨神经脱髓鞘化。通过臭氧，抑制了小脑活化，并减少了脊髓背角中c-Fos和降钙素基因相关肽（CGRP）的表达。本研究证明，臭氧通过上调AMPK-SOCS3轴以抑制TF表达来缓解CIPN，具有潜力成为CIPN的治疗方法。

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe adverse reaction to chemotherapeutics, which seriously affects the outcome of chemotherapy and patients' quality of life. Although it is commonly seen, it lacks effective treatment. Our previous study found that ozone could alleviate neuropathic pain. Damage-associated molecular patterns (DAMPs) or Toll-like receptor 4 (TLR4) or tissue factor (TF)-mediated neuroinflammation and microcirculation disturbance is the main reason for CIPN. Suppressors of cytokine signaling (SOCS) 3 is an endogenous negative feedback regulator of inflammation via TLR4 inhibition.Oxaliplatin (L-OHP) was used to establish mice's CIPN model. Nociceptive responses were assessed by observing the ICR mice's incidence of foot regression in mechanical indentation response experiments. Cell signaling assays were performed by Western blotting and immunohistochemistry. The mouse leukemia cells of monocyte-macrophage line RAW 264.7 were cultured to investigate the effects of ozone administration on macrophage.Ozone decreased the expression of TF in the blood and sciatic nerve. It upregulated the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-SOCS3 axis to relieve CIPN and inhibit TF expression in vivo. SOCS3 expression was induced by ozone to inhibit the p38/TF signaling in RAW 246.7 cells. Ozone also prevented L-OHP-induced sciatic nerve demyelination. Microglia activation was inhibited, and c-Fos and calcitonin gene-related peptide (CGRP) expression was decreased in the spinal dorsal horn via ozone.In this study, we demonstrated that ozone could alleviate CIPN by upregulating the AMPK-SOCS3 axis to inhibit TF expression, which is a potential treatment for CIPN.