調控巨噬細胞的表現型態減緩類風濕性關節炎造成的疼痛;Modulation of phenotypic diversity of macrophages attenuates rheumatoid arthritis induced mechanical hyperalgesia

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题名:	調控巨噬細胞的表現型態減緩類風濕性關節炎造成的疼痛;Modulation of phenotypic diversity of macrophages attenuates rheumatoid arthritis induced mechanical hyperalgesia
作者:	江澔;Jiang, Hoa
贡献者:	生命科學系
关键词:	巨噬細胞;類風濕性關節炎;macrophages;rheumatoid arthritis
日期:	2018-07-20
上传时间:	2018-08-31 11:37:00 (UTC+8)
出版者:	國立中央大學
摘要:	類風濕性關節炎(RA)是一種自體免疫疾病，其特徵在於慢性關節炎症導致骨頭侵蝕和軟骨損傷。RA 患者經常伴隨著持續性疼痛，並將疼痛改善作為首要任務。目前 RA 患者的治療著重於抑制炎症，在減緩慢性疼痛方面並沒有顯著的效果。治療 RA 引發的疼痛仍然是臨床實踐中的主要挑戰。我用發炎性疼痛模式動物篩選了小分子化合物和胜肽類藥物用於止痛效果。初步篩選後，我選擇小分子藥物NSC745885和Peptide X 用於 RA 模式小鼠做進一步測試。在 RA 模式小鼠中，腹腔注射 NSC745885 可以透過促發炎表型巨噬細胞(M1)的數量下降和抗發炎表型巨噬細胞(M2)的數量增加而減少 RA 誘導的機械性痛覺過敏。口服低劑量的 Peptide X 可以減少 RA 誘導的機械性痛覺過敏，推測可能是通過減少 M1 巨噬細胞和血液中 IL-6 的濃度。;Rheumatoid arthritis (RA), an autoimmuedisease, is characterized by chronic joint inflammation leading to bone erosion and cartilage damage. RA patients often have persistent pain and declare pain as the greatest problem. Current treatments focusing on suppression of inflammation may produce an inadequate response in relieving chronic pain in many RA patients. The treatment of RA pain continues to be a major management challenge in clinical practice. I have screened small molecule compounds and peptides for analgesic effects using inflammatory pain animal models. After pre-screening, I have identified compound NSC745885 and Peptide X for further tests on RA models. In RA model, intraperitoneal administration of NSC745885 reduced RA-induced mechanical hyperalgesia, probably through a decline in the number of pro-inflammatory phenotype macrophage (M1) and an increase in the number of anti-inflammatory phenotype macrophage (M2). Oral delivery of low dose of Peptide X reduced RA-induced mechanical hyperalgesia, probably by the reduction of the number of M1 macrophage and IL-6 level.
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