断藤益母汤对胶原诱导性关节炎模型小鼠的防治作用

Preventive and Therapeutic Effects of Duanteng Yimu Decoction on Mice with Collagen-induced Arthritis

目的观察断藤益母汤(DTYMD)对胶原诱导性关节炎(CIA)模型小鼠关节炎症及骨质破坏的防治作用。方法将48只雄性DBA/1J小鼠随机分为6组,每组8只,分别为正常组、模型组、MTX组(2 mg·kg^-1)、DTYMD低剂量组(7.5 g·kg^-1)、DTYMD中剂量组(15 g·kg^-1)、DTYMD高剂量组(30 g·kg^-1)。除正常组外,其他5组均采用二次免疫法复制CIA模型。加强免疫当天(Day21)开始灌胃给药,每日1次(MTX组每周灌胃给药2次),连续给药4周。Day21开始,每4d进行1次关节指数评分;给药结束后,取小鼠踝关节行micro-CT扫描并进行三维重建;小鼠踝关节行HE染色并进行关节病理评分。结果与正常组比较,模型组小鼠关节肿胀明显,严重者出现强直;踝关节骨质侵蚀明显,关节完整性受破坏严重;踝关节结构破坏严重,炎症细胞浸润明显,滑膜增生,血管翳形成,向软骨内侵袭导致软骨及骨破坏;关节周围炎症评分、骨破坏评分及病理总评分均明显升高(P<0.01)。与模型组比较,DTYMD各剂量组小鼠的关节红肿减轻,关节活动尚可;各剂量组均可显著降低CIA模型关节指数(P<0.01),其中高剂量组明显优于其他各组(P<0.01);各剂量组均可不同程度减轻踝关节骨质侵蚀破坏,高剂量组的骨质情况接近正常组,明显优于其他各组;各剂量组的踝关节相对完整,滑膜增厚不明显,少量炎症细胞浸润,关节周围炎症评分、骨破坏评分、病理总评分均显著降低(P<0.05,P<0.01)。结论 DTYMD能有效防治CIA模型小鼠的关节炎症和骨质破坏,并存在一定量效关系。

Objective To observe the preventive and therapeutic effects of Duanteng Yimu decoction(DTYMD) on joint inflammation and bone erosion in mice with collagen-induced arthritis.Methods Male DBA/1 J mice were randomly divided into 6 groups with 8 mice in each group:normal group,model group and MTX group(2 mg·kg^-1),DTYMD low dose group(7.5 g·kg^-1),DTYMD medium dose group(15 g·kg^-1),DTYMD high dose group(30 g·kg^-1).Except for the normal group,mice in the other five groups were used to construct CIA models by secondary immunization.On the day of intensive immunization(Day 21),mice were intragastrically fed with drugs once a day(the MTX group was given twice a week) for 4 weeks.The joint index was scored every 4 days from Day 21.After the administration,the malleolus joints of the hindlimbs of the mice were taken for micro-CT scanning and threedimensional reconstruction,and the hindlimbs were stained with HE and the pathological scores of the joints were evaluated.Results Compared with the normal group,the model group mice had obvious joint swelling and severe ankylosis,obvious ankle bone erosion and serious destruction of joint integrity,obvious infiltration of inflammatory cells,synovial hyperplasia,pannus formation;and the score of periarticular inflammation,bone destruction score and total pathological score were significantly increased(P<0.01).Compared with the model group,the joint redness and swelling of mice in each dose group of DTYMD were alleviated.The joint motion of mice in each dose group were slightly improved;and the joint index of CIA model in high dose group was significantly lower than that in other groups(P<0.01).Bone erosion of mice’s ankle joints in each dose group were significantly lower than that in model and MTX groups(P<0.01),the bone condition in high dose group was close to that in normal group,which was significantly better than that in other groups.In each dose group,the ankle joints of mice were almost complete,synovial thickening was not obvious,some inflammatory cells infiltrated and periarticular inflammation score,bone destruction score,total pathological score were significantly decreased(P<0.05,P<0.01).Conclusion DTYMD can effectively prevent joint inflammation and bone destruction in CIA mice and this is in a dose-independent manner.