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橙皮苷甲基金樱素通过抑制免疫应答缓解新西兰白兔的脊柱结核。

Hesperidin methyl chalcone alleviates spinal tuberculosis in New Zealand white rabbits by suppressing immune responses.

机构信息

Department of Orthopaedics, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, People's Republic of China.

Department of Anesthesiology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, People's Republic of China.

出版信息

J Spinal Cord Med. 2020 Jul;43(4):532-539. doi: 10.1080/10790268.2018.1507805. Epub 2018 Aug 20.

Abstract

Spinal tuberculosis (ST) refers to tuberculosis resulted from infections of () in the spinal cord. Hesperidin methyl chalcone (HMC) is a flavonoid derivative from citrus fruits with anti-inflammatory properties. We aimed to investigate the efficacy of HMC in treating ST in New Zealand white rabbit model. Rabbits were infected in the sixth lumbar vertebral bodies with or without strain H37Rv followed by treatments with HMC. 10 weeks post treatments, the adjacent vertebral tissues were examined by hematoxylin-eosin staining. The expression levels of transcription factor κB (NF-κB) p65 and monocyte chemoattractant protein-1 (MCP-1/CCL2) in lymphocytes were determined using reverse transcription quantitative real-time PCR (RT-qPCR), Western blot and enzyme-linked immunosorbent assays (ELISA). The serum levels of interleukin (IL)-2, IL-4, IL-10 as well as interferon (IFN)-γ were also assessed using ELISA. Western blot was used to determine the effects of HMC on the phosphorylation of IKKα/β, p65, and IκBα in the signal transduction of NF-κB pathways. HMC significantly attenuated the granulation in adjacent vertebral bone tissues. The expression of p65, IL-4, IL-10, and MCP-1 was reduced. The NF-κB pathway was suppressed, in which the phosphorylation of IκBα, IKKα/β, and p65 was inhibited whereas the relative level of IκBα was increased. HMC could serve as a therapeutic option to effectively inhibit granulomas formation through downregulation of MCP-1, IL-4, IL-10, and NF-κB in the treatment of ST.

摘要

脊柱结核(ST)是指由脊髓()感染引起的结核病。橙皮苷甲基查尔酮(HMC)是一种来源于柑橘类水果的类黄酮衍生物,具有抗炎作用。我们旨在研究 HMC 治疗新西兰大白兔模型中 ST 的疗效。用或不用 株 H37Rv 感染第 6 腰椎体,然后用 HMC 进行治疗。治疗 10 周后,用苏木精-伊红染色法检查相邻椎骨组织。采用逆转录定量实时 PCR(RT-qPCR)、Western blot 和酶联免疫吸附试验(ELISA)检测淋巴细胞中转录因子κB(NF-κB)p65和单核细胞趋化蛋白-1(MCP-1/CCL2)的表达水平。采用 ELISA 法检测血清中白细胞介素(IL)-2、IL-4、IL-10 和干扰素(IFN)-γ的水平。Western blot 法用于检测 HMC 对 NF-κB 信号转导途径中 IKKα/β、p65 和 IκBα磷酸化的影响。HMC 显著减轻了相邻椎骨组织中的肉芽组织。p65、IL-4、IL-10 和 MCP-1 的表达减少。NF-κB 途径被抑制,其中 IκBα、IKKα/β 和 p65 的磷酸化被抑制,而 IκBα的相对水平增加。HMC 可作为一种治疗选择,通过下调 MCP-1、IL-4、IL-10 和 NF-κB,有效抑制 ST 中肉芽肿的形成。

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