四味健步汤通过调节NF-κB和MAPK信号通路改善紫杉醇诱导的小鼠疼痛性周围神经病变。
Siwei Jianbu decoction improves painful paclitaxel-induced peripheral neuropathy in mouse model by modulating the NF-κB and MAPK signaling pathways.
作者信息
Suo Jinshuai, Wang Man, Zhang Peng, Lu Yuting, Xu Rong, Zhang Ling, Qiu Siyan, Zhang Qiuyan, Qian Yangyan, Meng Jing, Zhu Jing
机构信息
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Department of pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Department of pharmacy, Nanjing University of Chinese Medicine, Nanjing, China - Department of Neurology and Neuroscience, Johns Hopkins School of Medicine, Baltimore, USA.
出版信息
Regen Med Res. 2020;8:2. doi: 10.1051/rmr/200001. Epub 2020 Oct 20.
BACKGROUND
Paclitaxel, a commonly used chemotherapeutic agent, is usually associated with peripheral neuropathy. Paclitaxel induced peripheral neuropathy (PIPN) can be dose limiting and may have detrimental influence on patients' quality of life. However, the mechanism of PIPN remains unclear. Medicinal herbs and their formulas might offer neuronal protection with their multitarget and integrated benefits in chemotherapy-induced peripheral neuropathy (CIPN). Siwei Jianbu decoction (J12) is a classic formula of traditional Chinese medicine which can promote blood circulation and treat diabetic nephropathy in clinical with the symptoms of weakness and pain.
METHODS
The effects of J12 were treated in C57BL/6 mice before injected with Paclitaxel.Behaviour studies: Measurement of mechanical hyperalgesia, thermal nociception and cold allodynia. On the last day at the end of week 6, DRGs were obtained from mice for western blot and immunohistochemical analysis containing NF-κB, p-ERK1/2 and p-SAPK/JNK protein expression. Quantitative real-time polymerase chain reaction: mRNA expression of NF-κB, IL-1β and TNF-α was analyzed. Additionally, the blood samples collected from the eye socket of the mouse were prepared to examine the levels of NF-κB, TNF-α, IL-6 and IL-1β using ELISA assay kits.
RESULTS
Hypersensitivity tests and pathology analysis have demonstrated that J12 could improve paclitaxel-induced peripheral pain. J12 acts by inhibiting the activation of (C-Jun N-terminal kinases) JNK, (extracellular signal-regulated kinase) ERK1/2 phosphorylation in (Mitogen-activated protein kinases) MAPK signaling pathway and the nuclear factor-κB (NF-κB) in C57BL/6 mice model, J12 also inhibits the production of inflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and IL-6.
CONCLUSION
The present study showed that J12 ameliorates paclitaxel-induced peripheral neuropathic pain.
背景
紫杉醇是一种常用的化疗药物，通常与周围神经病变相关。紫杉醇诱导的周围神经病变（PIPN）可能会限制剂量，并可能对患者的生活质量产生不利影响。然而，PIPN的机制仍不清楚。草药及其配方可能因其在化疗诱导的周围神经病变（CIPN）中的多靶点和综合益处而提供神经保护作用。四味健步汤（J12）是一种经典的中药配方，在临床上可促进血液循环并治疗糖尿病肾病，伴有虚弱和疼痛症状。
方法
在C57BL/6小鼠注射紫杉醇之前用J12进行处理。行为学研究：测量机械性痛觉过敏、热痛觉和冷异常性疼痛。在第6周结束的最后一天，从小鼠获取背根神经节用于蛋白质免疫印迹和免疫组织化学分析，检测含NF-κB、p-ERK1/2和p-SAPK/JNK蛋白表达。定量实时聚合酶链反应：分析NF-κB、IL-1β和TNF-α的mRNA表达。此外，采集从小鼠眼眶获得的血样，使用酶联免疫吸附测定试剂盒检测NF-κB、TNF-α、IL-6和IL-1β的水平。
结果
超敏反应测试和病理学分析表明，J12可改善紫杉醇诱导的周围疼痛。在C57BL/6小鼠模型中，J12通过抑制丝裂原活化蛋白激酶（MAPK）信号通路中的（c-Jun氨基末端激酶）JNK、（细胞外信号调节激酶）ERK1/2磷酸化以及核因子-κB（NF-κB）的激活来发挥作用，J12还抑制包括肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β）和IL-6在内的炎性细胞因子的产生。
结论
本研究表明J12可改善紫杉醇诱导的周围神经性疼痛。
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