27-羥基膽固醇加劇類風溼性關節炎的進程

Abstract

類風濕性關節炎是一種與多種細胞相關的全身性疾病，包括單核細胞，滑 膜細胞，內皮細胞和其他免疫細胞。類風濕性關節炎可能是心血管疾病的因子之一，因為在患者的關節滑液中發現與動脈粥樣化有相似的細胞組成，而27-羥基膽固醇(27-hydroxycholestrol, 27-HC)加劇動脈粥樣硬化。在關節炎的進程中，類風濕性關節炎滑膜纖維母細胞(rheumatoid arthritis synovial fibroblast, RASF)扮演重要的角色。本實驗希望藉由研究RASF 細胞是否會受到27-HC 的影響，以延伸探討肥胖和膽固醇代謝對類風濕性關節炎的影響。結果發現，27-HC 促進RASF 細胞的增殖，以及它會造成發炎介質(chemokine (C-C motif) ligand 2, CCL2)濃度的增加。在動物實驗中，我們發現高脂高膽固醇飲食及卵巢切除確實可以增加27-HC 在血漿中的濃度，進而加劇關節炎的進展，例如：發炎細胞的浸潤和滑膜細胞的增殖；而使用CYP27A1 抑制劑—阿那曲唑(anastrozole)的大鼠會減少關節炎的症狀。因此我們可以推測27-HC 會加劇類風濕性關節炎的進程。

Rheumatoid arthritis (RA) is a systemic disease that is regulated by multiple varieties of cells, including monocytes, synovial cells, endothelial cells and other immune cells. RA is also a risk factor for cardiovascular disease. A similar cellular composition to atheroma was found in the synovial fluid of the patient. 27-hydroxycholesterol (27-HC) exacerbates atherosclerosis. In arthritis, rheumatoid arthritis synovial cells (RASF) plays an important role in the process of RA. This experiment hopes to investigate whether RASF will be affected by 27-HC to explore obesity and cholesterol metabolism for rheumatoid arthritis impact. The result shows that 27-HC promoted the proliferation of RASF cells; caused an increase in the concentration of various inflammatory mediators. In animal experiments, it is found that the high fat diet can indeed aggravate the development of arthritis, the infiltration of inflammatory cells and the proliferation of synovial cells, while the rats used the anastrozole which is an inhibitor of CYP27A1 reduce symptoms of fatty liver and arthritis. As a result, we may conclude that 27-HC could exacerbate the progression of rheumatoid arthritis.