基于JNK信号通路探讨豨莶草对痛风性关节炎影响

Investigating the effects of Herba Siegesbeckiae on gouty arthritis based on JNK signaling pathway

目的基于JNK信号通路探讨豨莶草对痛风性关节炎影响。方法将48只SD大鼠随机分为对照组、模型组、SP600125组(JNK抑制剂)和豨莶草高(4 g/kg)、中(2 g/kg)、低(1 g/kg)组,对照组和模型组灌胃给予生理盐水,其他各组给予相应的药物,连续7天,第5天给药1 h后向大鼠膝关节腔注射尿酸钠建立痛风性关节炎模型,对照组不做处理,采用HE染色观察滑膜组织病理情况,ELISA检测大鼠血清中TNF-α,IL-1和IL-8含量,western bloting测定JNK和p-JNK蛋白含量和RTPCR测定c-jun、AP-1和NF-κB mRNA表达。结果与对照组比较,模型组炎性细胞浸润,滑膜细胞增生,成纤维细胞,SP600125组和不同浓度豨莶草组对滑膜组织炎性细胞浸润明显减少,滑膜细胞增生和成纤维细胞增生明显减轻;模型组大鼠血清中TNF-α,IL-1和IL-8含量明显增高,SP600125组和不同浓度豨莶草组血清中TNF-α,IL-1和IL-8含量明显降低;western bloting和RT-PCR结果显示模型组滑膜组织中JNK和p-JNK蛋白含量明显增加,AP-1、c-jun和NF-κB mRNA表达明显增加,不同浓度豨莶草组和SP600125组能够明显降低痛风性关节炎大鼠JNK和p-JNK蛋白含量及c-jun、AP-1和NF-κB mRNA表达。结论豨莶草能够改善急性痛风性关节炎症状,其可能机制是调控JNK信号通路异常激活。

Objective To investigate the effects of Herba Siegesbeckiae on gouty arthritis based on JNK signaling pathway.Method 48 SD rats were divided into control group（ CG）,model group（ MG）,SP600125 group（ SG）,JNK inhibitor group,and 4 g/kg,2 g/kg,1 g/kg Herba Siegesbeckiae groups（ HSG）. CG and MG were administrated normal saline and other groups received the corresponding drug for 7 days. On the fifth day,injection of sodium uric acid to rat knee joint cavity established Gout arthritis model one hour after administration,and the control group did not receive any treatment. HE staining was used to observe the pathological changes of synovial tissue. TNF-α,IL-8 and IL-1 in serum were detected by ELISA. The content of JNK and pJNK were determined using Western Blotting,and c-jun,AP-1,F-κB mRNA were determined using RT-PCR. Results Compared with the control group,inflammatory cell infiltration,synovial cell proliferation,fibroblast,and the contents of TNF-α,IL-1 and IL-8 increased significantly in the model group. Nevertheless,inflammatory cell infiltration,proliferation of synovial cells,fibroblasts and the contents of TNF-α,IL-1 and IL-8 in serum reduced significantly in the SP600125 group and Herba Siegesbeckiae groups of different concentrations. The result showed that JNK and p-JNK protein in synovial tissue significantly increased,AP-1,c-jun and NF-κB mRNA expression significantly increased in the model group,measured using Western blotting and RT-PCR,respectively. SP600125 group and Herba Siegesbeckiae groups of different concentrations could significantly reduce JNK and p-JNKprotein and c-jun,AP-1 and NF-κB mRNA expression. Conclusion Herba Siegesbeckiae improved the symptoms of gouty arthritis,and its possible mechanism is regulating the abnormal activation of JNK signaling pathway.