27羥基膽固醇對類風濕性關節炎的影響

Abstract

類風溼性關節炎是一種由多種細胞(包含單核細胞, 關節滑膜細胞,內皮細胞, 其他免疫細胞)共同調控的系統性疾病。類風溼性關節炎也是心血管疾病的危險因子。在病患的關節滑液中發現與atheroma有類似的細胞組成。27-hydroxycholesterol會加劇粥狀動脈硬化。而在關節炎之中，類風濕性關節炎滑液細胞(RASF)扮演著重要的腳色。本實驗希望探討HepG2(人類肝癌細胞株)在fatty acid的刺激下 sterol 27-hydroxylase (CYP27A1) 的調控，以及RASF是否會受到27-hydroxycholesterol的各種影響來探討肥胖及膽固醇代謝對於類風濕性關節炎的影響。實驗結果發現，人類肝癌細胞株在受到oleic acid(油酸)的刺激下，CYP27A1的蛋白表現上升。並且在培養液中的27HC含量上升。另外的實驗中，27HC會促進RASF細胞的增生；並且造成多種發炎介質的濃度上升。且在動物實驗中發現肥胖的飲食確實能加劇關節炎的發展，發炎細胞的浸潤與滑液細胞的增生，而抑制CYP27A1的藥物anastrozole使用的組別小鼠在脂肪肝與關節炎的症狀都有減輕。總結上述的發現，肥胖會使肝臟細胞脂質代謝改變而CYP27A1增加，並產生較多量的27HC，而27HC可能是造成關節炎加劇的原因。

Rheumatoid arthritis is a systemic disease that is regulated by a variety of cells, including monocytes, synovial cells, endothelial cells, and other immune cells. Rheumatoid arthritis 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 exacerbates atherosclerosis. In arthritis, rheumatoid arthritis synovial cells (RASF) play an important role. This experiment hopes to investigate the regulation of sterol 27-hydroxylase (CYP27A1) stimulated by fatty acid in HepG2 (human hepatocarcinoma cell line), and whether RASF will be affected by 27-hydroxycholesterol to explore obesity and cholesterol metabolism for rheumatoid arthritis. Impact. The experimental results showed that the protein expression of CYP27A1 was increased in human hepatoma cell lines stimulated by oleic acid (oleic acid). And the 27HC content in the culture solution increased. In another experiment, 27HC promoted the proliferation of RASF cells; and caused an increase in the concentration of various inflammatory mediators. And in animal experiments, it is found that the diet of obesity can indeed aggravate the development of arthritis, the infiltration of inflammatory cells and the proliferation of synovial cells, while the mice used in the anastrozole that inhibit CYP27A1 have symptoms of fatty liver and arthritis. Reduced. Summarizing the above findings, obesity will change the lipid metabolism of liver cells and increase CYP27A1, and produce a larger amount of 27HC, which may be the cause of arthritis.