Therapeutic effect of Fuzi decoction on adjuvant arthritis rats
Objective To observe the therapeutic effect of Fuzi decoction on adjuvant arthritis(AA)rats,and explore the influence of Fuzi decoction on the protein expression of inflammatory cytokines,tumor necrosis factor α(TNF-α),interleukin-17A(IL-17A)and phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)signaling pathway genes,so as to provide experimental basis for its clinical application.Methods The arthritis model was established by intradermal injection of Freund's complete adjuvant in the right hind paw of rats,and they were randomly divided into blank group,model group,hydroxychloroquine sulfate positive drug control group(42 mg·kg-1·d-1),low dose of Fuzi decoction group(2.678 g·kg-1·d-1),medium dose of Fuzi decoction group(5.355 g·kg-1·d-1),high dose of Fuzi decoction group(10.71 g·kg-1·d-1).After the success of modeling,the drug was given orally every day for 28 days.The general situation of rats before and after inflammation and the change of toe volume were observed.After the experiment,the HE staining method was used to observe the histopathological changes of the ankle.The contents of serum TNF-α,IL-6,IL-2 and IL-17A were detected by ELISA.The protein expressions of PI3K,AKT and mTOR in the synovial tissue of the ankle joint were detected by immunohistochemistry staining.Results On the 6th day after modeling,compared with the primary toe swelling(0.11±0.02)mL in the blank group,the primary toe swelling(2.20±0.66)mL in the model group was significantly increased,the difference was statistically significant(P＜0.01).On the 33rd day after administration,compared with the primary toe swelling degree of the model group(2.75±0.32)mL,the primary toe swelling degrees of the hydroxychloroquine sulfate positive drug control group and the low,medium and high dosage groups of Fuzi decoction were(0.58±0.18),(0.85±0.22),(0.65±0.17),and(0.46±0.13)mL,respectively;the differences were statistically significant(all P＜0.05).Histopathological observation of ankle joint showed that in the model group,the synovial membrane structure of ankle joint was destroyed,synovial cells proliferated,inflammatory cells infiltrated,pannus formed,extensive fibrous tissue hyperplasia,bone erosion and other phenomena.The pathological changes of ankle joint in the group with hydroxychloroquine sulfate and Fuzi decoction were improved to some extent.The level of TNF-α in the model group was 90.47(79.59-91.65)pg/mL,while that in the low,middle and high dosage groups of Fuzi decoction decreased to 43.72(23.73-64.54),32.12(24.45-36.93)and 29.39(22.41-39.73)pg/mL,respectively;the differences were statistically significant(all P＜0.05).The level of IL-17A in the model group was 2.20(2.03-2.45)pg/mL,while the level of IL-17A in the high dose group of Fuzi decoction was 1.01(0.59-1.44)pg/mL,and the difference was statistically significant(P＜0.01).Compared with the model group,the expression levels of PI3K and AKT protein in the synovial tissue of ankle joint in hydroxychloroquine sulfate positive drug control group and low,medium and high dose groups of Fuzi decoction were significantly decreased(F=11.435,11.104;all P＜0.05).Compared with the model group,the expression level of mTOR protein in ankle joint synovium of low and high doses of Fuzi decoction was significantly decreased and the differences were statistically significant(F=8.063,P＜0.05).Conclusion Fuzi decoction had a good therapeutic effect on AA rats;in that,it could significantly alleviate the degree of joint swelling and significantly improve the pathological changes of joints,which was related to the reduction of the production of inflammatory cytokines,TNF-α and IL-17A and the negative regulation of protein expression in PI3K/AKT/mTOR signaling pathway.
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