Drinking Hydrogen-Rich Water Alleviates Chemotherapy-Induced Neuropathic Pain Through the Regulation of Gut Microbiota.
Drinking Hydrogen-Rich Water Alleviates Chemotherapy-Induced Neuropathic Pain Through the Regulation of Gut Microbiota.
复制标题
饮用富氢水通过调节肠道微生物群减轻化疗引起的神经性疼痛。
DOI：
10.2147/jpr.s288289
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发表时间：
2021
影响因子：
2.7
通讯作者：
Yu Y
中科院分区：
文献类型：
--
作者：
Lian N;Shen M;Zhang K;Pan J;Jiang Y;Yu Y;Yu Y
化疗诱导的神经性疼痛（CINP）是化疗药物最常见的并发症之一，其限制了可能挽救生命的抗癌治疗的剂量和持续时间，并损害患者的生活质量。我们以前的研究已经报道了分子氢（H2）可以用于预防和治疗各种疾病。但其潜在机制仍不清楚。本研究的目的是探讨富氢水对CINP肠道菌群的影响。所有C57 BL/6 J小鼠分为4组：正常饮水注射生理盐水组（H2O + Saline）、正常饮水注射奥沙利铂组（H2O + OXA）、富氢饮水注射生理盐水组（HW + Saline）和富氢饮水注射奥沙利铂组（HW + OXA）。在富氢水处理后第0、5、10、15和20天测试小鼠的机械缩爪阈值。第20天，收集各组小鼠粪便进行微生物群落多样性和结构分析。采用酶联免疫吸附法（ELISA）检测大鼠背根神经节（DRG）、L4-6脊髓节段和血清中炎性细胞因子（TNF-α和IL-6）、氧化应激因子（OH-和ONOO-）、脂多糖（LPS）和Toll样受体4（TLR 4）的水平。Western印迹法检测TLR 4在背根节和脊髓中的表达。结果表明，富氢水可减轻奥沙利铂所致的痛觉过敏，减少肠道微生物多样性，改变肠道菌群结构，逆转炎症细胞因子和氧化应激的失衡，降低LPS和TLR 4的表达。富氢水可能通过影响肠道菌群的多样性和结构，进而影响LPS-TLR 4通路，从而缓解CINP，这为进一步研究提供了方向。
Chemotherapy-induced neuropathic pain (CINP) is one of the most common complications of chemotherapeutic drugs which limits the dose and duration of potentially life-saving anticancer treatment and compromises the quality of life of patients. Our previous studies have reported that molecular hydrogen (H2) can be used to prevent and treat various diseases. But the underlying mechanism remains unclear. The aim of the present study was to explore the effects of hydrogen-rich water on gut microbiota in CINP. All C57BL/6J mice were divided into 4 groups: The group fed with normal drinking water and injected with saline (H2O + Saline), the group fed with normal drinking water and injected with oxaliplatin (H2O + OXA), the group fed with hydrogen-rich water and injected with saline (HW + Saline), and the group fed with hydrogen-rich water and injected with oxaliplatin (HW + OXA). The mechanical paw withdrawal threshold of the mice was tested on days 0, 5, 10, 15 and 20 after hydrogen-rich water treatment. On day 20, feces of mice from different groups were collected for microbial community diversity and structure analysis. The levels of inflammatory cytokines (TNF-α and IL-6), oxidative stress factors (OH- and ONOO-), lipopolysaccharide (LPS) and Toll-like receptor 4 (TLR4) were detected in dorsal root ganglia (DRG), L4-6 spinal cord segments and serum by enzyme-linked immunosorbent assay. The expression of TLR4 in DRG and spinal cords was determined by Western blot. The results illustrated that hydrogen-rich water could alleviate oxaliplatin-induced hyperalgesia, reduce the microbial diversity and alter the structure of gut microbiota, reverse the imbalance of inflammatory cytokines and oxidative stress, and decrease the expression of LPS and TLR4. Hydrogen-rich water may alleviate CINP by affecting the diversity and structure of the gut microbiota, and then the LPS-TLR4 pathway, which provides a direction for further research.