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天麻素对长春新碱诱导的大鼠抗肿瘤治疗周围神经病变的保护作用。

Protective effect of gastrodin on peripheral neuropathy induced by anti-tumor treatment with vincristine in rat models.

机构信息

Third-Grade Pharmacology Laboratory on Traditional Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical Science College of China Three Gorges University, Yichang, PR China.

Institute of Hepatopancreatobilary Surgery, China Three Gorges University, Yichang, PR China.

出版信息

Drug Chem Toxicol. 2021 Jan;44(1):84-91. doi: 10.1080/01480545.2018.1547739. Epub 2018 Dec 17.

Abstract

Cancer is a common disease threatening human health, chemotherapy is widely used in clinical treatment of cancer, but chemotherapy-induced peripheral neuropathy (CIPN) has a relevant impact on life quality of cancer patients. Administration of gastrodin can relieve chronic pain to cancer patients with CIPN and attenuated the inflammatory response by reducing the expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). However, its exact molecular mechanisms remain unclear. In this study, we established an animal model of CIPN using Walker-256 breast cancer cell and vincristine. We found that the mechanical and thermal pain threshold of rats was decreased with treatment of vincristine. Using gastrodin could restore the mechanical and thermal threshold without interfering anti-tumor effect of vincristine. Gastrodin relieved CIPN by inhibiting activation of spinal microglia through Fractalkine (CX3CL1) and its receptor CX3CR1, then inhibited P38/mitogen-activated protein kinase (MAPK) signaling pathway and reduced the expression of inflammatory factor TNF-α and interleukin-1β (IL-1β). Taking together, our study demonstrated that gastrodin is a potential drug for the treatment of CIPN and likely to improve cancer patient's life quality.

摘要

癌症是一种威胁人类健康的常见疾病,化疗广泛应用于癌症的临床治疗,但化疗引起的周围神经病变(CIPN)会对癌症患者的生活质量产生相关影响。天麻素的给药可以缓解患有 CIPN 的癌症患者的慢性疼痛,并通过降低肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的表达来减轻炎症反应。然而,其确切的分子机制尚不清楚。在这项研究中,我们使用 Walker-256 乳腺癌细胞和长春新碱建立了 CIPN 动物模型。我们发现,长春新碱处理会降低大鼠的机械和热痛阈值。天麻素的给药可以恢复机械和热阈值,而不干扰长春新碱的抗肿瘤作用。天麻素通过抑制趋化因子(CX3CL1)及其受体 CX3CR1 激活脊髓小胶质细胞来缓解 CIPN,然后抑制 P38/丝裂原活化蛋白激酶(MAPK)信号通路并降低炎症因子 TNF-α和白细胞介素-1β(IL-1β)的表达。总之,我们的研究表明天麻素是治疗 CIPN 的一种潜在药物,可能会提高癌症患者的生活质量。

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