Zhang Xue-feng, Zhang Fan, Liu Hong-yu, Sun Guo-dong, Liu Zong-hong, Lü Hang, Chi Chao, Li Chun-yu
Department of Cardiac Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
Chin Med J (Engl). 2009 Jan 20;122(2):188-92.
Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a non-steroidal anti-inflammatory drug used as an adjuvant to sensitize cancer cells to apoptosis. However, in rats suffering from acute rejection, celecoxib reduced apoptosis of myocardial cells. We hypothesize that celecoxib reduces myocardial apoptosis either by inducing apoptosis in peripheral blood lymphocytes (PBLs) or by altering the percentage of CD4(+) and CD8(+) lymphocytes.
After cardiac transplantation, rats were administered intragastrically with celecoxib (50 mg/kg per day) for 3, 5 or 7 days, at which time the graft was excised and evaluated for organ rejection. In addition, PBLs were isolated from the blood to determine PBLs apoptosis, and the percentage of CD4(+) and CD8(+) lymphocytes.
Celecoxib induced PBLs apoptosis in 3 days, but protected the cells from apoptosis at 5 and 7 days. Also, the percentage of CD4(+) lymphocytes decreased only at 3 days, but a reduction in the percentage of CD8(+) lymphocytes was not seen until 7 days after the transplant surgery. Celecoxib only decreased acute rejection at 5 days, with no discernible difference in rejection after 3 and 7 days.
The results suggested that celecoxib displayed a multiple physiological function in a time-dependent manner.
塞来昔布是一种选择性环氧化酶-2(COX-2)抑制剂,是一种非甾体抗炎药,用作辅助药物使癌细胞对凋亡敏感。然而,在遭受急性排斥反应的大鼠中,塞来昔布减少了心肌细胞的凋亡。我们假设塞来昔布通过诱导外周血淋巴细胞(PBL)凋亡或改变CD4(+)和CD8(+)淋巴细胞的百分比来减少心肌凋亡。
心脏移植后,给大鼠灌胃塞来昔布(每天50 mg/kg),持续3、5或7天,此时切除移植物并评估器官排斥反应。此外,从血液中分离出PBL以确定PBL凋亡以及CD4(+)和CD8(+)淋巴细胞的百分比。
塞来昔布在3天时诱导PBL凋亡,但在5天和7天时保护细胞免于凋亡。此外,CD4(+)淋巴细胞的百分比仅在3天时下降,但直到移植手术后7天CD8(+)淋巴细胞的百分比才降低。塞来昔布仅在5天时降低急性排斥反应,在3天和7天后排斥反应无明显差异。
结果表明塞来昔布以时间依赖性方式表现出多种生理功能。