目的：研究血栓素A2受体（thromboxane A2 receptor， TXA2R）作为环氧酶2（cyclooxygenase-2， COX-2）下游产物对类风湿关节炎（rheumatoid arthritis，RA）滑膜细胞增殖力和COX-2表达的影响。方法：利用细胞增殖与毒性检测试剂盒（MTS）检测TXA2R拮抗剂SQ29548和激动剂U46619对RA关节滑膜细胞MH7A增殖力的影响作用，并用real-time PCR检测它们对COX-2 mRNA表达的影响；利用BrdU细胞增殖检测法观察MH7A细胞在转染COX-2小干扰RNA（small interfering RNA， siRNA）后细胞增殖受抑制的情况及额外施加U46619的可能影响。结果：SQ29548和U46619分别具有抑制和促进MH7A细胞增殖力与COX-2 mRNA表达的作用，且U46619可在一定程度上重建由COX-2 siRNA所抑制的MH7A细胞增殖力。结论：TXA2通过其受体TXA2 R既可控制COX-2的表达，又可介导COX-2的细胞增殖效应，有可能作为RA治疗较为理想的新靶标。%AIM:To examine the effects of thromboxane A 2 receptor ( TXA2 R) , the downstream product of cy-clooxygenase-2 (COX-2), on the proliferative ability and COX-2 expression in rheumatoid arthritis (RA) synovial cells. METHODS:The effects of TXA2 R antagonist SQ29548 and agonist U46619 on the proliferation of RA synovial cell line MH7A were detected by MTS cell proliferation assay , and their effects on COX-2 mRNA expression in MH7A cells were al-so examined by real-time PCR.In addition, the possible effect of U46619 on the proliferation of MH7A cells, when COX-2 was knocked down by siRNA , was determined by BrdU cell proliferation assay .RESULTS:SQ29548 inhibited the cell proliferation and the mRNA level of COX-2 while U46619 enhanced them.Moreover, U46619 reconstitute the proliferative ability of MH7A cells to some extent that inhibited by COX-2 siRNA.CONCLUSION: In RA synovial cells, TXA2R is able to control COX-2 expression, while it also mediates the effects of COX-2, suggesting that TXA2R might be an ideal candidate for RA treatment .
展开▼
