CCK-8对TNF-α诱导大鼠RSC-364细胞MMPs/TIMP-1的影响  

Effect of CCK-8 on expression of MMPs/TIMP-1 in TNF-α-induced RSC-364

作　　者：徐锦荣[1,2] 丛斌[1] 李淑瑾[1] 金玉怀[3] 赵占胜[1] 

机构地区：[1]河北医科大学法医系河北省法医学重点实验室,河北石家庄050017 [2]河北医科大学第三医院免疫风湿科,河北石家庄050051 [3]河北医科大学病原学教研室,河北石家庄050017

出　　处：《中国药理学通报》2017年第4期567-571,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30470679);河北省自然科学基金资助项目(No C2005000705)

摘　　要：目的研究八肽胆囊收缩素(CCK-8)对TNF-α诱导的大鼠RSC-364细胞MMPs/TIMP-1的影响。方法采用ELISA观察TNF-α作用下CCK-8对RSC-364细胞MMP-3、-9、-1及TIMP-1分泌的影响,比较MMP-3、-9、-1和TIMP-1比值变化,用RT-PCR观察CCK-8对TNF-α作用下RSC-364细胞MMP-3、-9 mRNA表达的影响。结果静息和CCK-8单独孵育细胞后未检测到MMP-3和MMP-9,产生少量MMP-1和TIMP-1,表达MMP-3和MMP-9 mRNA甚微,CCK-8有抑制TNF-α诱导细胞MMP-3、-9、-1分泌和MMP-3、-9 mRNA表达的作用,并且降低TNF-α所致的MMPs/TIMP-1比值的上升。结论 CCK-8下调MMPs基因表达,减少MMPs分泌,使MMPs与TIMP-1比值下降,从而降低MMPs活性,表明CCK-8能调节滑膜细胞分泌功能,提示CCK-8在类风湿关节炎发病过程中可能具有调控作用。Aim To observe the influence of CCK-8 on expression of MMPs/TIMP-1 in TNF-α-induced rat fibroblast-like synovial cell line RSC-364.Methods The secretion levels of MMP-1,MMP-3,MMP-9 and TIMP-1 were determined using ELISA;MMP-3 and MMP-9 mRNA expressions were detected by RT-PCR.Results MMP-3 and MMP-9 could not be examined in RSC-364 incubated with CCK-8 and unstimulated RSC-364,which was able to product a little MMP-1,TIMP-1 and express even less MMP-3,-9 mRNA.CCK-8 inhibited the increase in MMP-1,MMP-3,MMP-9 secretion and MMP-3,-9 mRNA expression in TNF-α-induced RSC-364.TIMP-1 production was also increased in TNF-α-induced RSC-364.CCK-8 had no effect on TIMP-1 production in TNF-α-induced RSC-364,but was able to reduce the ratios of MMP-1,MMP-3,MMP-9 to TIMP-1.Conclusion The inhibitory effect of CCK-8 on MMPs activity may be related to the decrease of MMPs mRNA expression,MMPs secretion and the ratios of MMPs to TIMP-1 in TNF-α-induced RSC-364,which indicates that CCK-8 might be a possible regulator in the pathogenesis of rheumatoid arthritis.

关 键 词：八肽胆囊收缩素 TNF-Α 关节炎 成纤维样滑膜细胞 基质金属蛋白酶 金属蛋白酶组织抑制剂 

分 类 号：R-322[医药卫生] R345.9