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预防奥沙利铂诱导的神经性疼痛:使用黄连素抑制大鼠背根神经节中NF-κB的激活和促炎细胞因子的释放。

Preventing oxaliplatin-induced neuropathic pain: Using berberine to inhibit the activation of NF-κB and release of pro-inflammatory cytokines in dorsal root ganglions in rats.

作者信息

Ni Wan, Zheng Xiaolan, Hu Ling, Kong Chao, Xu Qingbang

机构信息

Department of Pain Medicine, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei 434020, P.R. China.

Department of Gastroenterology, The Fifth People's Hospital of Wuhan City, Wuhan, Hubei 430050, P.R. China.

出版信息

Exp Ther Med. 2021 Feb;21(2):135. doi: 10.3892/etm.2020.9567. Epub 2020 Dec 10.

Abstract

Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a serious, undesirable effect of cancer treatment which is particularly difficult to prevent. Berberine and its derivatives have been reported to display robust antioxidant and analgesic effects in rat models of diabetic neuropathic pain and peripheral nerve injury. However, the analgesic role of berberine on oxaliplatin-induced CIPNP remains unknown. The present study aimed to explore the analgesic effect of berberine on CIPNP. Sprague Dawley rats were used to create the CIPNP animal model by oxaliplatin administration. Behavioral tests were performed by von Frey test, acetone drop test, hot plate test, and motor coordination. The protein expression levels of NF-κB p65 and phosphorylated p65 in dorsal root ganglions (DGRs) were detected by western blot analysis. Finally, TNF-α and IL-6 levels in DRGs were measured using specific ELISA kits. The results from the behavioral analysis demonstrated that a single injection of berberine ameliorated the mechanical and cold allodynia and thermal hyperalgesia in the model rats in a dose-dependent manner. Cumulative administration of berberine prevented the mechanical and cold allodynia and thermal hyperalgesia in the development of CIPNP induced by oxaliplatin. This prophylactic effect of berberine was associated with reduced phosphorylation of p65 and with decreased levels of pro-inflammatory cytokines IL-6 and TNF-α. The present study indicated that berberine may have a role in preventing the development of CIPNP and may serve as a therapeutic compound for the treatment of CIPNP.

摘要

化疗引起的周围神经性疼痛(CIPNP)是癌症治疗中一种严重的不良效应,尤其难以预防。据报道,黄连素及其衍生物在糖尿病性神经病理性疼痛和周围神经损伤的大鼠模型中具有强大的抗氧化和镇痛作用。然而,黄连素对奥沙利铂诱导的CIPNP的镇痛作用尚不清楚。本研究旨在探讨黄连素对CIPNP的镇痛作用。通过给Sprague Dawley大鼠注射奥沙利铂建立CIPNP动物模型。采用von Frey试验、丙酮滴注试验、热板试验和运动协调性试验进行行为学测试。通过蛋白质印迹分析检测背根神经节(DGRs)中NF-κB p65和磷酸化p65的蛋白表达水平。最后,使用特异性ELISA试剂盒检测DRGs中TNF-α和IL-6的水平。行为分析结果表明,单次注射黄连素可剂量依赖性地改善模型大鼠的机械性和冷觉异常性疼痛以及热痛觉过敏。黄连素的累积给药可预防奥沙利铂诱导的CIPNP发展过程中的机械性和冷觉异常性疼痛以及热痛觉过敏。黄连素的这种预防作用与p65磷酸化的降低以及促炎细胞因子IL-6和TNF-α水平的降低有关。本研究表明,黄连素可能在预防CIPNP的发展中发挥作用,并可能作为治疗CIPNP的一种治疗性化合物。

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