Objective: To observe the effect of moxibustion on phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin protein (PI3K/Akt/mTOR) signaling pathway in the foot-pad synovial tissue in rats with rheumatoid arthritis (RA), and to explore the mechanism of moxibustion for treating RA.
Methods: Forty healthy SD rats were randomly divided into a control group, a model group, a moxibustion group, a cigarette-moxibustion group and a medication group, 8 rats in each group. The RA model was established with subcutaneous injection of complete Freund's adjuvant (CFA) in the left hind foot-pad under wind, cold and wet environment in the model group, the moxibustion group, the cigarette-moxibustion group and the medication group. The rats in the moxibustion group were treated with moxibustion at "Zusanli" (ST 36) for 20 min; the rats in the cigarette-moxibustion group were treated with moxibustion of ordinary cigarette at "Zusanli" (ST 36) for 20 min; the rats in the medication group were treated with tripterygium glycosides suspension (0.8 mg/100 g) by gavage. All the intervention was given once a day for 15 days. The left hind foot-pad volume was measured before and after modeling and after 15-day intervention. After 15-day intervention, the serum levels of IL-17 and IL-23 were detected by ELISA method, and the expression levels of PI3K, Akt and mTOR in synovial tissue of left hind foot-pad were detected by Western blot method.
Results: The volume of left hind foot-pad, the serum levels of IL-23 and IL-17 and the expression of PI3K, Akt and mTOR in synovial tissue of left hind foot-pad in the model group were higher than those in the control group (P<0.01). After intervention, the volume of left hind foot-pad and the expression of PI3K, Akt and mTOR protein in synovium tissue in the moxibustion group and medication group were lower than those in the model group (P<0.01, P<0.05), while the serum levels of IL-17 and IL-23 in the moxibustion group were lower than those in the model group (P<0.01). The volume of left hind foot-pad, the serum levels of IL-23 and the expression of mTOR protein in synovial tissue in the moxibustion group were lower than those in the medication group (P<0.01, P<0.05), while the volume of left hind foot-pad, the serum levels of IL-23 and the expression of PI3K, Akt and mTOR protein in synovium tissue in the moxibustion group were lower than those in the cigarette-moxibustion group (P<0.01).
Conclusion: Moxibustion may play a therapeutic effect on RA by inhibiting the level of IL-23, IL-17 and the activity PI3K/Akt/mTOR, and regulating inflammatory response and autophagy.
目的：观察艾灸对类风湿性关节炎（RA）模型大鼠足跖滑膜组织磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白（PI3K/Akt/mTOR）信号通路的影响，探索艾灸治疗RA的作用机制。方法：将40只健康SD大鼠随机分为对照组、模型组、艾灸组、香烟灸组和药物组，每组8只。除对照组外，其余4组采用风、寒、湿环境因素结合左后足跖皮下注射完全弗氏佐剂（FCA）建立RA模型。艾灸组予艾灸左侧“足三里”20 min；香烟灸组以普通卷烟灸左侧“足三里”20 min；药物组予雷公藤多苷片混悬液（0.8 mg/100 g）灌胃。均每日1次，共干预15 d。造模前后及干预15 d后测量左后足跖容积；干预15 d后采用ELISA法检测血清白介素（IL）-17、IL-23含量，Western blot法检测左后足跖滑膜组织PI3K、Akt、mTOR蛋白表达水平。结果：干预后模型组大鼠左后足跖容积，血清IL-23、IL-17含量及左后足跖滑膜组织PI3K、Akt、mTOR蛋白表达水平均高于对照组(P<0.01)；艾灸组和药物组大鼠干预后左后足跖容积和滑膜组织PI3K、Akt、mTOR蛋白表达水平均低于模型组(P<0.01，P<0.05)，艾灸组血清IL-17、IL-23含量低于模型组(P<0.01)；艾灸组大鼠左后足跖容积、血清IL-23含量与左后足跖滑膜组织mTOR蛋白表达水平低于药物组(P<0.01，P<0.05)，艾灸组左后足跖容积、血清IL-23含量与左后足跖滑膜组织PI3K、Akt、mTOR蛋白表达水平低于香烟灸组(P<0.01)。结论：艾灸可能通过抑制IL-23、IL-17水平与PI3K/Akt/mTOR信号通路活性，调节炎性反应与自噬活动，发挥对RA的治疗效应。.
Keywords: PI3K/Akt/mTOR signaling pathway; autophagy; inflammatory reaction; moxibustion; rheumatoid arthritis.