塞来昔布对膝关节炎大鼠肿瘤坏死因子α信号通路及关节滑膜细胞的影响

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

目的:探究塞来昔布对膝关节炎大鼠肿瘤坏死因子α(TNF-α)信号通路及关节滑膜细胞的影响。方法:SD大鼠随机分为模型组、假手术组和治疗组,治疗组大鼠制作膝关节炎模型后给予塞来昔布进行治疗。通过TUNEL法、qRT-PCR法、CCK-8法、免疫印迹等方法检测3组大鼠滑膜细胞凋亡情况、TNF-αmRNA表达含量、TNF-α蛋白含量、关节炎指数及细胞增殖情况。结果:模型组、治疗组、假手术组关节滑膜细胞凋亡率分别为89.38%、46.84%、13.68%。模型组与假手术组、治疗组相比较,细胞凋亡率显著升高,治疗组细胞凋亡数量多于假手术组。假手术组、治疗组细胞增殖OD值比模型组高,差异具有统计学意义,假手术组关节滑膜细胞的增殖数量最多,模型组关节滑膜细胞的增殖数量最少,治疗组关节滑膜细胞的增殖情况比假手术组相比明显减少。与假手术组、治疗组比较,模型组关节滑膜细胞中TNF-α蛋白表达水平显著上升,治疗组TNF-α蛋白表达水平较假手术组明显升高。与假手术组、治疗组比较,模型组TNF-αmRNA含量显著升高,治疗组TNF-αmRNA表达量较假手术组明显升高。治疗组和模型组大鼠关节炎指数相近,随着给药时间的增加,治疗组大鼠膝关节炎情况逐渐好转,而未服用药物的模型组大鼠病情逐渐恶化。结论:塞来昔布胶囊治疗膝关节炎大鼠效果显著,能够显著降低TNF-α信号通路的表达水平,改善关节滑膜细胞的凋亡情况。

Objective:To investigate the effects of celecoxib on TNF-αsignaling pathway and synovial cells in rats with knee arthritis.Methods:The selected SD rats were divided into model group,sham group and treatment group with 6 rats in each group.Rats in the model group were made into models of knee arthritis;rats in the treatment group were made into models of knee arthritis and then treated with celecoxib.TUNEL,qRT-PCR,CCK-8 and Western blotting were used to detect the apoptosis,TNF-αmRNA expression,TNF-αprotein content and proliferation in rats of the three groups so as to explore the effects of celecoxib on TNF-αsignaling pathway and synovial cells in rats with knee arthritis.Results:The results showed that the apoptotic rates of synovial cells in the model group,treatment group,and sham group were 89.38%,46.84%and 13.68%,respectively.The apoptosis rate of the model group was significantly higher than that of the sham group and the treatment group.The number of apoptotic cells in the treatment group was significantly more than that of sham group.The OD value of cell proliferation in sham group and treatment group was higher than that of the model group,and there was significant difference between groups.The proliferation of joint synovial cells in sham group was the highest,and the number of synovial cells in the model group was the least.The proliferation of synovial cells was significantly reduced compared with the sham group.Compared with the sham group,the expression of TNF-αprotein in the synovial cells of the joints was significantly higher than that in the sham group.The expression of TNF-αmRNA in the model group was significantly higher than that in the sham group and the treatment group.The arthritis index of the rats in the treatment group and the model group was similar.With the increase of the administration time,the knee arthritis gradually improved in the treatment group,but worsened in the model group in which rats didn’t take celecoxib.Conclusion:Celecoxib capsules have significant effects on the treatment of knee arthritis in rats by significantly reducing the expression of TNF-αsignaling pathway and improving the apoptosis of synovial cells in the knee joint.