黑骨藤追风活络胶囊调节NF-κB/STAT3/mPGES-1信号通路改善胶原诱导性关节炎的作用研究

Mechanism of Heiguteng Zhuifenghuoluo Capsule regulating NF-κB/STAT3/mPGES-1 signaling pathway in treating collagen-induced arthritis

目的:研究黑骨藤追风活络胶囊(Heiguteng Zhuifenghuoluo cupsule,HZC)调节NF-κB/STAT3/mPGES-1信号通路改善胶原诱导性关节炎(Collagen induced arthritis,CIA)大鼠的作用机制。方法:取24只SD大鼠,随机分组为正常组、模型组、HZC组和甲氨蝶呤(methotrexate,MTX)组。除正常组外,其余三组采用牛Ⅱ型胶原和完全弗氏佐剂混合乳化剂构建类风湿性关节(rheumatoid arthritis,RA)大鼠模型。按照实验分组分别给予生理盐水、MTX(1 mg/kg)和HZC(243 mg/kg)灌胃,共给药21天。每周测量大鼠足肿胀程度、观察并进行足肿胀评分、检测大鼠血清中前列腺素E 2(Prostaglandin E2,PGE 2),检测大鼠滑膜组织中微粒体前列腺素E2合酶-1(microsomal prostaglandin E synthase 1,mPGES-1)以及p-p65、p-STAT3蛋白表达情况。结果:模型组大鼠足肿胀程度、肿胀程度评分、大鼠血清PGE 2明显增加,HZC和MTX组大鼠足肿胀程度、肿胀程度评分和大鼠血清PGE 2明显降低。进一步机制研究发现模型组大鼠关节滑膜组织中mPGES-1、p-p65、p-STAT3蛋白的表达增加,HZC和MTX组大鼠关节滑膜组织中mPGES-1、p-p65、p-STAT3蛋白的表达明显降低。结论:HZC通过抑制NF-κB/STAT3/mPGES-1信号通路,发挥其对胶原诱导性关节炎(CIA)大鼠的治疗作用。

This study explored the mechanism of Heiguteng Zhuifenghuoluo Cupsule(HZC)regulating NF-κB/STAT3/mPGES-1 signaling pathway in treating collagen-induced arthritis(CIA).Twenty-four SD rats were randomly divided into the normal group,the model group,the HZC group and the methotrexate(MTX)group.Except for the normal group,rheumatoid arthritis(RA)model rats were constructed with bovine type II collagen and complete Freund's adjuvant mixed emulsifier.The rats were given normal saline,MTX(1 mg/kg)and HZC(243 mg/kg)by gavage for 21 days according to the experimental groups.The foot swelling degree of the rats was measured weekly,the foot swelling score(AI),the prostaglandin E 2(PGE 2)in serum,and the expression of microsomal prostaglandin E synthase 1(mPGES-1),p-p65 and p-STAT3 proteins in synovial tissues of the rats were detected.The foot swelling degree,the foot swelling score,and the level of serum PGE 2 in the model group significantly increased,while those in the HZC and MTX groups significantly decreased.The expression of mPGES-1,p-p65 and p-STAT3 proteins in the synovial tissues of the model group increased,while those in the HZC and MTX groups decreased.In conclusion,HZC exerts its therapeutic effect on collagen-induced arthritis(CIA)rats by inhibiting the NF-κB/STAT3/mPGES-1 signaling pathway.