血栓素A2受体通过介导环氧酶2的合成增强类风湿关节炎滑膜细胞的增殖作用

 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TXA2R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。

Thromboxane A2 receptor induces proliferation of rheumatoid arthritis synovial cells by up-regulation of cyclooxygenase-2

AIM：To examine the effects of thromboxane A2 receptor (TXA2R), the downstream product of cyclooxygenase-2 (COX-2), on the proliferative ability and COX-2 expression in rheumatoid arthritis (RA) synovial cells. METHODS：The effects of TXA2R 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 also 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.