塞来昔布对类风湿关节炎大鼠肿瘤坏死因子-α信号通路及滑膜细胞的影响

Effect of celecoxib on tumor necrosis factor-αsignaling pathway and synovial cells in rats with rheumatoid arthritis

目的:探讨塞来昔布对类风湿关节炎(RA)大鼠肿瘤坏死因子-α(TNF-α)信号通路及滑膜细胞的影响。方法:将大鼠分为正常对照组,建立RA模型(RA组),建立RA模型后灌胃塞来昔布(实验组),RA组及实验组大鼠建立RA大鼠模型,检测大鼠关节炎症指数后,通过多种方法检测病理、滑膜细胞凋亡、TNF-α蛋白水平及阳性表达。结果:23 d、30 d时与RA组相比,实验组关节炎症指数显著降低,且RA组、实验组关节炎症指数显著高于对照组;对照组滑膜细胞呈单层生长,未出现增生,关节腔内无渗透,未见明显炎症。RA组滑膜组织出现坏死,大量炎症表达,明显滑膜增生,软骨损伤。实验组经塞来昔布灌胃处理后,滑膜增生减少,只见少量炎症浸润;对照组滑膜细胞凋亡率为6.65%,高于RA组1.73%,实验组滑膜细胞凋亡率为14.65%,高于RA组;对照组滑膜组织中TNF-α表达量少于RA组,实验组滑膜组织中TNF-α表达量少于RA组。结论:塞来昔布能改善RA大鼠关节炎症指数,促进滑膜细胞坏死,降低TNF-α表达,改善病情。

Objective:To explore the effects of celecoxib on tumor necrosis factor-alpha(TNF-α)signaling pathway and synovial cells in rats with rheumatoid arthritis(RA).Methods:Rats were equally divided into normal control,RA model and celecoxib(CE)treated groups,among which RA rats in CE treated group were treated intragastrically with celecoxib and rats in other two groups were intragastrically administered with normal saline.The arthritis index of all rats were evaluated and pathological changes,apoptosis of synovial cells,expression of TNF-αwere detected.Results:During experimental course,arthritis indexes of rats in both model and celecoxib treated groups were significantly higher than those in normal control.And,intragastric administration of celecoxib led to statistical decrease in arthritis index on day 23 and 30 compared to those in model rats treated with normal saline.The synovial cells of normal rats displayed single layer without hyperplasia,and exudation and inflammation were undetected.On the contrary,necrosis,severe inflammation and hyperplasia of synovial tissue accompanying with cartilage injury were observed in RA model rats.However,intragastric administration of celecoxib statistically weakened hyperplasia of synovial tissue,and slight inflammatory infiltration was detectable in experimental rats.Apoptosis rate of synovial cells in celecoxib treated rats was 14.65%,which was significantly higher than those in RA rats(1.73%)and normal control rats(6.65%).And,expression of TNF-αin synovial tissue of celecoxib treated rats was statistically lower than those in either RA model and normal control rats.Conclusion:Celecoxib could improve symptoms of RA partly due to its ability to weaken arthritis index,accelerate necrosis of synovial cells and downregulate expression of TNF-α.