清热祛湿法对尿酸钠关节炎大鼠OPG/RANKL/NF-κB信号通路调控的影响

Effects of OPG/RANKL/NF-κB signaling pathway in sodium urate-induced arthritis rats by clearing heat and eliminating dampness method

目的:观察清热祛湿法对尿酸钠关节炎大鼠OPG/RANKL/NF-κB信号通路的影响。方法:检测大鼠受试踝关节周长变化值。用ELISA法测定大鼠血清IL-12、IL-6、TNF-α、OPG、RANKL的含量以及滑膜组织中NF-κB p65蛋白的表达变化。结果:与正常组比较,模型组大鼠受试踝关节周长显著增加(P<0.01),血清IL-12、IL-6、TNF-α及RANKL的含量显著升高(P<0.01),血清中OPG的含量及OPG/RANKL显著降低(P<0.01),滑膜组织中NF-κB p65蛋白表达显著升高(P<0.01);与模型组比较,中药低、中、高剂量组大鼠受试踝关节周长显著降低(P<0.05),血清IL-12、IL-6、TNF-α及RANKL的含量显著降低(P<0.05),而血清中OPG的含量及OPG/RANKL显著升高(P<0.05);滑膜组织NF-κB p65蛋白表达显著降低(P<0.05)。结论:自拟痛风方抑制急性痛风关节炎性反应可能与降低血清中IL-12、IL-6、TNF-α、RANKL含量,并上调血清中OPG的分泌及OPG/RANKL,降低滑膜组织中NF-κB p65蛋白表达有关。

Objective： To observe the effect of clearing heat and eliminating dampness method on OPG/RANKL/NF-κB signaling pathway in sodium urate-induced arthritis rats. Methods： Detecting changes in the circumference of the ankle in rats. Through the establishment of experimental rats, intragastric administration, extraction（anesthesia, blood collection, centrifugation, serum collection, and synovial membrane）, ELISA was used to determine the contents of IL-12, IL-6, TNF-α OPG, RANKL in serum and expression of NF-κB p65 protein in synovial tissue. Results： Compared with the normal group, the circumference of ankle in the test were significantly increased（P〈0.01）, the levels of serum IL-12, IL-6, TNF-α and RANKL in the model group were significantly higher（P〈0.01）, and the content of OPG and OPG/RANKL were significantly lower（P〈0.01）, the expression of NF-κB p65 protein in the synovial tissue of the model group was significantly higher（P〈0.01）. Compared with the model group, the circumference of ankle in the test were significantly decreased（P〈0.05）, the serum levels of IL-12, IL-6, TNF-α and RANKL in the rats in the high, middle and low dose groups of self-made Tongfeng Formula were significantly lower（P〈0.05）, while the serum OPG levels and OPG/RANKL were significantly increased（P〈0.05）, and the expression of NF-κB p65 protein was significantly decreased（P〈0.05）. Conclusion： Selfmade Tongfeng Formula in inhibiting acute gout arthritis may decrease serum levels of IL-12, IL-6, TNF-α, RANKL, upregulate OPG secretion and OPG/RANKL in serum, and decrease NF-κB p65 protein expression in synovial tissue.