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Abstract：
This study aimed to evaluate the therapeutic potential of amantadine in a vincristine-induced peripheral neuropathy model in rats. Forty-eight male Wistar rats were used. The treated groups received oral amantadine at doses of 2, 5, 12, 25 and 50 mg/kg, with daily applications for 14 days. The mechanical paw withdrawal threshold was measured using a digital analgesimeter. Immunohistochemical analysis of IL-6, TNFα, MIP1α, IL-10, CX3CR1, CXCR4, SOD, CAT and GPx, and enzymatic activity analysis of CAT, SOD and GPx were performed, in addition to quantitative PCR of Grp78, Chop, Ho1, Perk, Bax, Bcl-xL, Casp 3, Casp 9, IL-6, IL-10, IL-18 and IL-1β. The results showed an increase in nociceptive thresholds in animals that received 25 mg/kg and 50 mg/kg amantadine. Immunohistochemistry showed a decrease in the immunostaining of IL-6, TNFα, MIP1α and CX3CR1, and an increase in IL-10. CAT and SOD showed an increase in both immunochemistry and enzymatic analysis. qPCR revealed a reduced expression of genes related to endoplasmic reticulum stress and regulation in the expression of immunological and apoptotic markers. Amantadine demonstrated antinociceptive, anti-inflammatory and antioxidant effects in the vincristine-induced peripheral neuropathy model in rats, suggesting that amantadine may be considered an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.
摘要：
本研究旨在评估金刚烷胺在长春新碱诱导的大鼠周围神经病变模型中的治疗潜力。使用48只雄性Wistar大鼠。治疗组口服金刚烷胺，剂量为2、5、12、25和50mg/kg，每天申请14天。使用数字止痛药测量机械爪缩回阈值。IL-6，TNFα的免疫组织化学分析，MIP1α,IL-10、CX3CR1、CXCR4、SOD、CAT和GPx，和CAT的酶活性分析，进行SOD和GPx，除了Grp78的定量PCR，Chop，Ho1,Perk,Bax,Bcl-xL,Casp3、Casp9、IL-6、IL-10、IL-18和IL-1β。结果显示接受25mg/kg和50mg/kg金刚烷胺的动物的伤害性阈值增加。免疫组织化学显示IL-6，TNFα的免疫染色降低，MIP1α和CX3CR1，以及IL-10的增加。CAT和SOD在免疫化学和酶分析中均显示出增加。qPCR显示与内质网应激相关的基因表达减少，免疫和凋亡标志物的表达受到调节。金刚烷胺表现出抗伤害感觉，长春新碱诱导的大鼠周围神经病变模型的抗炎和抗氧化作用,提示金刚烷胺可能被认为是治疗长春新碱引起的周围神经性疼痛的替代方法。
