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塞来昔布对骨关节炎患者CD8+CD28-调节性T细胞分泌细胞因子动力的影响
作者:陈海斌1  武宇航2  范宝莹2  宁晔1  麦惠强1 
单位:1. 中山市人民医院 急诊科, 广东 中山 528400;
2. 中山市人民医院 骨二科, 广东 中山 528400
关键词:骨关节炎 CD8+CD28-调节性T细胞 细胞因子 塞来昔布 
分类号:R453;R681
出版年·卷·期(页码):2019·47·第三期(264-269)
摘要:

目的:探讨CD8+CD28-调节性T细胞(Treg)在骨关节炎(OA)发病机制中的作用及塞来昔布(CLX)对该细胞分泌细胞因子动力的影响。方法:选取OA合并关节腔积液患者52例作为观察组,以36例创伤性关节炎(TA)合并关节腔积液患者及31例健康体检者(HD)作为标本对照,通过流式细胞术检测外周血及关节腔积液内CD8+CD28- Treg含量,及其胞内细胞因子转化生长因子β1(TGF-β1)及白介素10(IL-10)的百分含量;分析首诊时OA患者关节腔积液上述三者与血沉(ESR)、C反应蛋白(CRP)及疼痛视觉评分(VAS)的相关性;分别向CD8+CD28- Treg培养液加入CLX(n=27)及双氯芬酸钠(DS,n=25),观察刺激前后分泌TGF-β1及IL-10的变化。分别使用CLX及DS治疗OA患者,观察两组8周后CD8+CD28- Treg、TGF-β1及IL-10的差异。结果:(1)OA患者外周血CD8+CD28- Treg、IL-10及TGF-β1三者均显著低于TA及HD,且关节腔积液内三者同样低于TA组(P<0.05);(2)相关性分析显示OA患者首诊时关节腔内CD8+CD28- Treg、IL-10及TGF-β1三者当中任意一项均与SER、CRP及VAS三者当中任意一项呈显著负相关性(均为P<0.05);(3)分别使用CLX及DS与关节液内CD8+CD28- Treg共同培养5d,发现第120小时两组CD8+CD28- Treg、IL-10及TGF-β1均较第48小时显著上升,以CD8+CD28- Treg最为显著(P<0.05),且CLX组48h及96h的CD8+CD28- Treg含量同样高于DS组(P<0.05)。(4)治疗8周后,CLX及DS患者CD8+CD28- Treg、IL-10及TGF-β1含量均较治疗前明显回升,且CLX组三者显著高于DS组(P<0.05)。结论:外周血及关节腔积液内CD8+CD28- Treg、IL-10及TGF-β1降低是OA患者的重要免疫学表现,且与炎症及疼痛程度相关;CLX及DS均可增强CD8+CD28- Treg分泌IL-10及TGF-β1的动力,但效果以CLX优于DS,该效应在用药5d后尤为明显。

Objective:To explore the effect of celecoxib(CLX) on the secreting dynamics of the cytokines produced by CD8+CD28- regulatory T cells(Treg) in patients with osteoarthritis(OA). Methods:Fifty-two patients with OA, together with 36 patients with traumatic arthritis(TA) and 31 healthy persons, were enrolled. Flow cytometry(FCM) was used to test the levels of CD8+CD28- T cells and their intracellular cytokines, the transforming growth factor beta-1(TGF-β1) and interleukin 10(IL-10). The correlations between synovial levels of CD8+CD28- T cells, IL-10, and TGF-β1 and ESR, CRP, and VAS, were analyzed at initial diagnosis for OA. CD8+CD28- T cells were cultured for 5 days and CLX(n=27) was administrated into the culture solution, so were diclofenac sodium (DS, n=25). The levels of CD8+CD28- T cells, IL-10, and TGF-β1 were tested by FCM at the time points of 48 h, 72 h, 96 h, and 120 h after culture. Oral CLX or DS was taken by the OA patients for 8 weeks, and the levels of CD8+CD28- T cells, IL-10, and TGF-β1 were tested at the end of treatment.Results:(1) The levels of peripheral blood CD8+CD28- T cells, IL-10, and TGF-β1 in the OA patients were significantly lower than those in the TA or healthy ones (all P<0.05), and the same differences were found in the synovial liquid (all P<0.05). (2) Correlation analysis showed that any one of synovial levels of CD8+CD28- T cells, IL-10, and TGF-β1 was significantly related to any one of ESR, CRP, and VAS (all P<0.05). (3) Synovial levels of CD8+CD28- T cells, IL-10, and TGF-β1 at the 120 h were apparently higher than those at 48 h for both CLX and DS group, especially the CD8+CD28- T cells (all P<0.05). Synovial levels of CD8+CD28- T cells, IL-10, and TGF-β1 at both 48 h and 96 h were higher in the CLX group when compared to the DS one (P<0.05). (4) The levels of CD8+CD28- T cells, IL-10, and TGF-β1 at the end of 8th weeks were higher than those pre-treatment for the both groups, but the three levels were significantly higher in the CLX group when compared with the DS one (P<0.05). Conclusion:Decreased levels of CD8+CD28- T cells, IL-10, and TGF-β1 in both peripheral blood and synovial liquid were the vital feature for OA patients, and the levels were related to the severity of inflammation and pain. Both CLX and DS can enhance the secreting dynamics of IL-10 and TGF-β1, but better effect is found in CLX, particularly on the 5th day after administration.

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