吴门芪藤汤对大鼠膝骨关节炎成纤维样滑膜细胞氨基末端激酶的影响

Observing the Effect of Wumenqiteng Decoction on the Expression of JNK Pathways of Arthritis Rat

目的:通过观察吴门芪藤汤对弗氏完全佐剂(CFA)诱导的大鼠膝骨关节炎(KOA)模型关节成纤维样滑膜细胞炎性细胞因子表达以及c-Jun氨基末端激酶(JNK)通路活化的影响,探讨吴门芪藤汤治疗膝骨关节炎的抗炎和抑制成纤维样滑膜细胞过度凋亡的作用机制。方法:采用CFA诱导的KOA大鼠模型为研究对象,各给药组分别用SP600125(JNK抑制剂)和吴门芪藤汤灌胃干预后,观察原代培养的成纤维样滑膜细胞中白介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)、基质金属蛋白酶-3(MMP-3)表达差异以及细胞凋亡和JNK通路的活化情况。结果:与模型组比较,吴门芪藤汤组明显降低成纤维样滑膜细胞原代培养上清中IL-1β,TNF-α及MMP-3含量水平,差异有统计学意义(P<0.05);显著抑制成纤维样滑膜细胞过度凋亡,差异有统计学意义(P<0.01);显著抑制成纤维样滑膜细胞JNK通路蛋白的磷酸化,差异有统计学意义(P<0.001)。结论:吴门芪藤汤通过降低CFA诱导的KOA大鼠成纤维样滑膜细胞分泌炎性细胞因子水平减弱JNK通路活化,进而抑制滑膜组织过度凋亡,这可能是其治疗膝骨关节炎潜在的机制之一。

Objective:Through the investigating the effect of Wumenqiteng decoction on the expression of inflammatory factor in fibroblast-like synoviocytes and JNK pathways of CFA(complete Freund’s adjuvant)induced arthritis rat model,to explore the mechanism of Wumenqiteng decoction for the treatment of anti-inflammatory and inhibits excessive apoptosis of fibroblast-like synovial cells of osteoarthritis of the knee.Methods:The CFA induced arthritis rat model was regarded as the study subject,SP600125(JNK inhibitor)and Wumenqiteng decoction were used in each experiment group for gastric intervention.To observe the expression differences of interleukin 1β(IL-1β),tumor necrosis factorα(TNF-α),matrix metalloproteinase-3(MMP-3)and cell apoptosis and the activation of JNK pathway on the original cultured synovial cells.Results:Compared with the model group,the expression of IL-1β,TNF-αand MMP-3 in the supernatant were obviously decreased of primary culture fibroblast-like synoviocytes compound with the Wumenqiteng decoction group(P<0.05),and the cell apoptosis in fibroblast-like synoviocytes were significantly reduced(P<0.01),the protein phos-phorylation of JNK pathway in fibroblast-like synoviocytes was significantly inhibited by Wumenqiteng decoction peroral treatment(P<0.001).Conclusion:Wumenqiteng decoction can reduce the activation of JNK pathway by reducing inflammatory cytokine levels of fibroblast-like synoviocytes in CFA induced arthritis rat model,so as to inhibit the excessive apoptosis of synovial tissue,which might be the potential mechanism in the treatment of osteoarthritis of the knee.