SIC1a开放诱导大鼠关节软骨细胞基质代谢失衡的作用及机制研究
SIC1a contributes to the matrix metabolism imbalance of articular chondrocytes induced by extracellular acidosis
目的：研究ASIC1a开放对胞外酸化诱导的AA大鼠关节软骨细胞代谢失衡的作用及部分机制。方法：实验分正常组（pH 7.4）、pH 6.0、特异性阻断剂PcTX-1、沉默组、非特异性阻断剂Amiloride处理的酸化组，对二甲基亚甲蓝分光法检测大鼠关节软骨细胞培养上清中GAG的含量，氯胺T法检测HYP的含量，ELISA法检测MMP-2、TIMP-2的含量。Western blot 法检测酸化及阻断ASIC1a后ERK1/2、p38MAPK磷酸化蛋白的表达。结果：阻断酸敏感离子通道后，能明显抑制胞外酸化引起的GAG、HYP和TIMP-2的水平降低(p<0.01)，对MMP-2的水平降低抑制作用较弱(p<0.01)。酸刺激能引起ERK1/2、p38MAPK磷酸化水平升高，阻断酸敏感离子通道后磷酸化水平升高受到抑制(p<0.01)。结论：ASIC1a参与了酸诱导的大鼠关节软骨细胞基质代谢的失衡，并且激活ERK1/2和p38MAPK信号通路，阻断ASIC1a能抑制基质代谢的失衡，减少AA大鼠关节软骨的损伤。
IM To study the effect of blocking ASIC1a on the cell metabolism of the rats articular chondrocytes with extracellular acidosis and its possible molecular mechanism. METHODS Establish and identify the ASIC1a-silencing model. The GAG content of cell culture supernatant was determined by dimethyl-methylene blue spectrophotometric assay, while HYP content by chloramine T assay. ELISA assay was used to measure MMP-2, TIMP-2 content. Furthermore, the ERK1/2, p38MAPK phosphorylation protein expression level were tested by western blot assay. RESULTS Blocking acid sensing ion channels could significantly inhibit the famous decrease of GAG, HYP and TIMP-2 levels induced by extracellular acidification, while the effect of MMP-2 was weaker. CONCLUSION Blocking ASIC1a could regulate rat articular chondrocyte matrix metabolism and thereby inhibit the AA rats articular cartilage damage induced by acidosis.
陈飞虎、葛金芳、唐杰、吴繁荣、胡伟
基础医学生理学生物化学
酸敏感离子通道1a类风湿关节炎2关节软骨细胞基质代谢丝裂原激活的蛋白激酶
cid sensing ion channel 1aRheumatoid arthritisArticular chondrocytesMatrix metabolismMitogen-activated protein kinase
陈飞虎,葛金芳,唐杰,吴繁荣,胡伟.SIC1a开放诱导大鼠关节软骨细胞基质代谢失衡的作用及机制研究[EB/OL].(2013-03-07)[2025-08-03].http://www.paper.edu.cn/releasepaper/content/201303-199.点此复制
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