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异甘草素通过抑制新西兰白兔模型中的免疫反应减轻脊柱结核。

Isoliquiritigenin attenuates spinal tuberculosis through inhibiting immune response in a New Zealand white rabbit model.

作者信息

Wang Wenjing, Yang Baozhi, Cui Yong, Zhan Ying

机构信息

Record Room, Jinan Second People's Hospital, Jinan 250011, Shandong, China.

Department of Obstetrics & Gynaecology, Jinan Second People's Hospital, Jinan 250011, Shandong, China.

出版信息

Korean J Physiol Pharmacol. 2018 Jul;22(4):369-377. doi: 10.4196/kjpp.2018.22.4.369. Epub 2018 Jun 25.

Abstract

Spinal tuberculosis (ST) is the tuberculosis caused by () infections in spinal curds. Isoliquiritigenin 4,2',4'-trihydroxychalcone, ISL) is an anti-inflammatory flavonoid derived from licorice (), a Chinese traditional medicine. In this study, we evaluated the potential of ISL in treating ST in New Zealand white rabbit models. In the model, rabbits (n=40) were infected with strain H37Rv or not in their 6 lumbar vertebral bodies. Since the day of infection, rabbits were treated with 20 mg/kg and 100 mg/kg of ISL respectively. After 10 weeks of treatments, the adjacent vertebral bone tissues of rabbits were analyzed through Hematoxylin-Eosin staining. The relative expression of Monocyte chemoattractant protein-1 (MCP-1/CCL2), transcription factor κB (NF-κB) p65 in lymphocytes were verified through reverse transcription quantitative real-time PCR (RT-qPCR), western blotting and enzyme-linked immunosorbent assays (ELISA). The serum level of interleukin (IL)-2, IL-4, IL-10 and interferon γ (IFN-γ) were evaluated through ELISA. The effects of ISL on the phosphorylation of IκBα, IKKα/β and p65 in NF-κB signaling pathways were assessed through western blotting. In the results, ISL has been shown to effectively attenuate the granulation inside adjacent vertebral tissues. The relative level of MCP-1, p65 and IL-4 and IL-10 were retrieved. NF-κB signaling was inhibited, in which the phosphorylation of p65, IκBα and IKKα/β were suppressed whereas the level of IκBα were elevated. In conclusion, ISL might be an effective drug that inhibited the formation of granulomas through downregulating MCP-1, NF-κB, IL-4 and IL-10 in treating ST.

摘要

脊柱结核(ST)是由脊柱结核感染引起的结核病。异甘草素(ISL),即4,2',4'-三羟基查耳酮,是一种从中药甘草中提取的具有抗炎作用的黄酮类化合物。在本研究中,我们评估了ISL在新西兰白兔模型中治疗脊柱结核的潜力。在该模型中,40只兔子的6个腰椎椎体被感染或未感染H37Rv菌株。自感染之日起,兔子分别接受20mg/kg和100mg/kg的ISL治疗。治疗10周后,通过苏木精-伊红染色分析兔子相邻椎体骨组织。通过逆转录定量实时PCR(RT-qPCR)、蛋白质免疫印迹法和酶联免疫吸附测定(ELISA)验证淋巴细胞中单核细胞趋化蛋白-1(MCP-1/CCL2)、转录因子κB(NF-κB)p65的相对表达。通过ELISA评估血清白细胞介素(IL)-2、IL-4、IL-10和干扰素γ(IFN-γ)水平。通过蛋白质免疫印迹法评估ISL对NF-κB信号通路中IκBα、IKKα/β和p65磷酸化的影响。结果显示,ISL可有效减轻相邻椎体组织内的肉芽组织。MCP-1、p65以及IL-4和IL-10的相对水平恢复正常。NF-κB信号传导受到抑制,其中p65、IκBα和IKKα/β的磷酸化受到抑制,而IκBα水平升高。总之,在治疗脊柱结核方面,ISL可能是一种通过下调MCP-1、NF-κB、IL-4和IL-10来抑制肉芽肿形成的有效药物。

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