加味宣痹汤对急性痛风性关节炎大鼠TLR4/MyD88/IRAK4通路的作用机制

Mechanism of modified Xuanbi Decoction in treating acute gouty arthritis rats via TLR4/MyD88/IRAK4 pathway

目的:探讨加味宣痹汤治疗急性痛风性关节炎(AGA)的效果及相关作用机制。方法:采用高尿酸血症(HUA)联合AGA的造模方法,以加味宣痹汤对照秋水仙碱作为干预手段。评测干预后各组大鼠左踝关节炎症指数、足肿胀情况;并在取材后,观察大鼠左踝关节滑膜组织形态学炎性病理情况,检测血清中尿酸(SUA)、C-反应蛋白(CRP)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)浓度,以及左踝关节液中TLR4、MyD88、IRAK4 mRNA表达水平。结果:治疗4次后,加味宣痹汤各剂量组大鼠炎症指数、足肿胀水平均显著低于模型组(P<0.05)。与模型组比较,加味宣痹汤各剂量组大鼠血清SUA、CRP、IL-1β、TNF-α水平和关节液TLR4、MyD88、IRAK4 mRNA表达水平显著降低(P<0.05),且加味宣痹汤中、高剂量组大鼠上述指标均低于秋水仙碱组(P<0.05)。HE染色病理切片显示,秋水仙碱组和加味宣痹汤各剂量组大鼠踝关节滑膜组织中炎性细胞数量和血管充血现象明显较少,其中高剂量组与正常组最接近。结论:加味宣痹汤对HUA合并AGA大鼠具有一定的抗炎、消肿、降尿酸作用,其可能是通过抑制TLR4、MyD88、IRAK4的活化,使TNF-α、IL-1β等炎症因子减少释放,从而发挥作用。

Objective: To explore the effect and mechanism of modified Xuanbi Decoction in treating acute gouty arthritis(AGA). Methods: Hyperuricemia(HUA) combined with AGA was used as the model, and modified Xuanbi Decoction were used as the intervention method to control colchicine. The inflammatory index and foot swelling of left ankle in rats were evaluated after intervention were evaluated in each group. After sampling, the synovial tissue morphology and inflammatory pathology of the left ankle joint were observed, and the serum concentrations of SUA, CRP, IL-1β and TNF-α, as well as mRNA expressions of TLR4, MyD88 and IRAK4 in the left ankle joint fluid were detected. Results: After 4 times of treatment, the levels of the inflammatory index and foot swelling in the modified Xuanbi Decoction group were significantly lower than those in the model group(P<0.05). Compared with the model group, SUA, CRP, IL-1β, TNF-α levels and mRNA expression levels of joint fluid TLR4, MyD88 and IRAK4 were significantly lower than those in the modified Xuanbi Decoction group(P<0.05), and the above indexes in the medium and high dose modified Xuanbi Decoction groups were lower than those in the colchicine group(P<0.05). HE staining pathological sections showed that the number of inflammatory cells and vascular congestion in synovial tissue of the ankle joint of the colchicine group and the modified Xuanbi Decoction all dose groups were significantly less, among which the pathological morphology of synovial tissue of the high-dose modified Xuanbi Decoction group was the closest to that of the normal group. Conclusion: Modified Xuanbi Decoction has the effect of anti-inflammation, reducing swelling and decreasing uric acid on HUA and AGA rats, which may play a role by inhibiting the activation of TLR4, MyD88 and IRAK4 and reducing the release of inflammatory factors TNF-α and IL-1β.