电针通过减轻活性氧介导的NLRP3炎性小体过度激活来改善痛风性关节炎疼痛。
Electroacupuncture improves gout arthritis pain via attenuating ROS-mediated NLRP3 inflammasome overactivation.
作者信息
Wei Huina, Liu Boyu, Yin Chengyu, Zeng Danyi, Nie Huimin, Li Yuanyuan, Tai Yan, He Xiaofen, Liu Boyi
机构信息
Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
出版信息
Chin Med. 2023 Jul 18;18(1):86. doi: 10.1186/s13020-023-00800-1.
BACKGROUND
Gout results from disturbed uric acid metabolism, which causes urate crystal deposition in joints and surrounding tissues. Gout pain management is largely limited to colchicine and nonsteroidal anti-inflammatory drugs. Constant usage of these medications leads to severe side effects. We previously showed electroacupuncture (EA) is effective for relieving pain in animal model of gout arthritis. Here we continued to study the mechanisms underlying how EA alleviates gout pain.
METHODS
Monosodium urate was injected into ankle joint to establish gout arthritis model in mice. EA or sham EA was applied at ST36 and BL60 acupoints of model animals. Biochemical assays, immunostaining, live cell Ca imaging and behavioral assays were applied.
RESULTS
Model mice displayed obvious mechanical allodynia, accompanied with gait impairments. EA attenuated mechanical hypersensitivities and improved gait impairments. EA reduced the overexpression of NLRP3 inflammasome signaling molecules in ankle joints of model animals. EA-induced anti-allodynia, as well as inhibition on NLRP3 inflammasome, were mimicked by antagonizing but abolished by activating NLRP3 inflammasome via pharmacological methods. EA attenuated oxidative stress, an upstream signaling of NLRP3 inflammasome in ankle joints of model mice. Exogenously increasing oxidative stress abolished EA's inhibitory effect on NLRP3 inflammasome and further reversed EA's anti-allodynic effect. EA reduced neutrophil infiltrations in ankle joint synovium, a major mechanism contributing to oxidative stress in gout. Pharmacological blocking NLRP3 inflammasome or EA reduced TRPV1 channel overexpression in dorsal root ganglion (DRG) neurons. Ca imaging confirmed that EA could reduce functional enhancement in TRPV1 channel in DRG neurons during gout.
CONCLUSIONS
Our results demonstrate that EA reduces gout pain possibly through suppressing ROS-mediated NLRP3 inflammasome activation in inflamed ankle joints and TRPV1 upregulation in sensory neurons, supporting EA as a treatment option for gout pain.
背景
痛风是由尿酸代谢紊乱引起的，会导致尿酸盐晶体沉积在关节和周围组织中。痛风疼痛的管理主要局限于秋水仙碱和非甾体抗炎药。持续使用这些药物会导致严重的副作用。我们之前表明电针（EA）对缓解痛风性关节炎动物模型的疼痛有效。在此，我们继续研究EA缓解痛风疼痛的潜在机制。
方法
将尿酸钠注射到小鼠踝关节以建立痛风性关节炎模型。对模型动物的足三里穴（ST36）和昆仑穴（BL60）进行电针或假电针治疗。采用生化分析、免疫染色、活细胞钙成像和行为分析等方法。
结果
模型小鼠表现出明显的机械性痛觉过敏，并伴有步态障碍。电针减轻了机械性超敏反应并改善了步态障碍。电针降低了模型动物踝关节中NLRP3炎性小体信号分子的过表达。通过药理学方法拮抗NLRP3炎性小体可模拟电针诱导的抗痛觉过敏以及对NLRP3炎性小体的抑制作用，但激活NLRP3炎性小体则可消除这种作用。电针减轻了氧化应激，氧化应激是模型小鼠踝关节中NLRP3炎性小体的上游信号。外源性增加氧化应激消除了电针对NLRP3炎性小体的抑制作用，并进一步逆转了电针的抗痛觉过敏作用。电针减少了踝关节滑膜中的中性粒细胞浸润，这是痛风中氧化应激的主要机制。药理学阻断NLRP3炎性小体或电针可降低背根神经节（DRG）神经元中TRPV1通道的过表达。钙成像证实电针可降低痛风期间DRG神经元中TRPV1通道的功能增强。
结论
我们的结果表明，电针可能通过抑制炎症踝关节中ROS介导的NLRP3炎性小体激活和感觉神经元中TRPV1上调来减轻痛风疼痛，支持电针作为痛风疼痛的一种治疗选择。
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