| Objectives:In order to investigate the effect of genistein(gen)on the secretion of proinflammatory cytokines and anti-inflammatory cytokines secreted by rats with CIA(collagen induced arthritis).Subject:The rats with CIAMethods:Sixty Sprague-Dawley rats were randomly divided into6groups:normal group,model group,low-dose genistein(Gen) treatment group,moderate-dose Gen treatment group,high-dose Gen treatment group and methotrexate(MTX) group(n=10).Model group and all treatment groups were induced CIA model in SD rats immunized by subcutaneous injection of collagen type II combined with complete Freund’s adjuvant(CFA).On the second day after the injection,1ml of suspension of different concentration of gen(50μM,100μM,200μM,once a day for35days)and MTX(0.1mg/ml body weight,once a week)were administered by oral gavage respectively.The rats in normal group and model group were administrated with normal saline in the same volume.The arthritis was scored once a week with the arthritis index(AI)and hind paw swelling.After the treatment for5weeks,the rats were sacrificed,and the knee joints were harvested for pathological examination, and sera were immediately separated from3ml of blood samples collected from the abdominal veins in serum tubes.The plasma concentrations of interleukin-4(IL-4),IL-6,IL-8,IL-10,tumor growth factor-P1(TGF-β1),and lymphotoxin-a(LT-a)were determined with enzyme-linked immunosorbent assay (ELISA).Results:1、Joint swelling in the rats with CIA established with collagen type Ⅱ combined with complete Freund’s adjuvant were observed apparently three days later.AI score,hind paw swelling,and pathological detection were shown significant differences between the model group and the control group, indicating that the model of CIA rats was constructed successfully.2、The serum level of IL-6,IL-8,LT-a in the CIA model group was significantly higher than in the control group(P<0.05),while Gen could down-regulate the secretion of IL-6，IL-8and LT-a,which is supported by the observation that Gen at high dose had the similer inhibition of the secretion of IL-6,JI-8relative to MTX group,and the inhibition of LT-a in all Gen treatment groups was weaker than that in MTX group.3、The serum level of cytokines IL-4,IL-10,and TGF-β1in the CIA model group was significantly lower than in the control group (P0<0.05), while Gen could up-regulate the secretion of IL-4,IL-10,and TGF-β1,which is supported by the findings that similar up-regulation of the secretion of IL-4in moderate-dose Gen treatment group and IL-10in high-dose treatment Gen group was observed relative to MTX group,moreover,A significant induction in the secretion of TGFβ1was seen in CIA rats treatment with high doses, as compared with that in MTX group.Conclusions:1、 In the pathogenesis of CIA rats, the pro-inflammatory cytokines release are significantly increased,and the anti-inflammatory cytokines secretion are significantly decreased, suggesting that these cytokines may be the important factors involved in the pathological process of RA.2、 The secretion of IL-6, IL-8and LT-a was decreased, while the secretion of IL-4,IL-10and TGF-β1was increased after treatment with Gen,suggesting that Gen can inhibit the release of inflammatory factors,and increase the expression of anti-inflammatory cytokines in RA,and ameliorate the arthromeningitis of CIA rats.3、 Gen at high dose had the similer inhibition of the secretion of IL-6,IL-8relative to MTX group,and the inhibition of LT-a in all Gen treatment groups was weaker than that in MTX group; similar up-regulation of the secretion of IL-4in moderate-dose Gen treatment group and IL-10in high-dose treatment Gen group was observed relative to MTX group, moreover, A significant induction in the secretion of TGF-β1was seen in CIA rats treatment with high doses, as compared with that in MTX group. |
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