摘要
Abstract
AIM:To observe the role and its possible mechanism of inflammatory cytokines of IL-1 β and TNF α which plays an important role in the etiology of MTX on RA.METHODS:The establishment of animal model of rheumatoid arthritis with collagen type Ⅱ,with MTX (0.2 mg/kg/W) treatment,the rats were killed after six weeks,serum for detection of IL-1β and TNF-α; separation of knee joint synovial cells in rats (FLS) were cultured,identification,detection of LPS induced FLS in the culture supernatant of IL-1β and TNF-α,and observes the effect of MTX on the secretion of IL-1β and TNF-α of FLS; adding different doses of MTX on the FLS culture,expression by Western Blot method for detection of FLS ERK protein and phosphorylation of protein.RESULTS:Arthritis index score and joint swelling and joint pathology showed determination modeling success,isolated synovial cells by flow cytometry FLS expression of VCAM-1 was 85.5％.After modeling,CIA rat serum IL-1 β and TNF-α increased obviously,there was significant difference compared with the blank control group (P＜0.05),MTX could effectively reduce the content of serum CIA in rats of IL-1 β and TNF-α (P＜ 0.05),but failed to recover to normal.In rats with CIA FLS MTX could inhibit LPS induced secretion of IL-1 β and TNF-α.Displayed in Western Blot detection,different concentrations of MTX on ERK protein expression of FLS in CIA rats compared with the model group showed no significant difference (P＞0.05).Expression of p-ERK CIA in FLS of rats was significantly higher than that in control group (P＜0.01),after the treatment of MTX,low dose group had no effect on the expression of p-ERK protein,while in the medial and high dose group could reduce the p-ERK protein (P ＜ 0.05).CONCLUSION:MTX has immunosuppressive effects at the same time through the inhibition of inflammatory cytokines IL-1 β and TNF-α,it also has anti-inflammatory effect.The mechanism may be partly related to inhibition of MAPK signaling pathway in ERK phosphorylation relate.关键词
类风湿关节炎/甲氨蝶呤/IL-1β/TNF-α/ERK/p-ERKKey words
rheumatoid arthritis/ methotrexate/ IL-1β/ TNF-α / ERK/p-ERK分类
医药卫生
