类风湿性关节炎热痹证大鼠模型的复制与评价

Replication and Evaluation of Rat Model of Rheumatoid Arthritis with Heat Arthralgia Syndrome

目的建立符合中医热痹证"红、肿、热、痛"证候特征的类风湿性关节炎(RA)病证结合大鼠模型并进行模型评价。方法将54只Wistar雌性大鼠随机分为3组,每组18只;正常组常规饲养,模型1组复制胶原诱导性关节炎(CIA)大鼠模型,模型2组在CIA基础上,给予风、湿、热环境刺激;采用关节炎指数(AI)、关节表面温度、热痛阈值和毛细血管通透性对模型进行评价。结果模型2组大鼠起病时间较模型1组早(P<0.05),但模型2组成模率(83%)与模型1组(78%)无统计学意义(P>0.05)。模型1组在第28天,模型2组在第21天和28天的AI>4分,表明两组模型均复制成功。模型2组与模型1组双侧关节表面均出现异常高温区,温度值显著升高(P<0.05),其中模型2组在第14天、21天和28天双侧关节表面温度均明显高于模型1组(P<0.05)。与正常组相比,模型1组第21天、28天,模型2组第14天、21天和28天热痛阈值均显著降低(P<0.05),但模型2组与模型1组热痛阈值只有第21天的差异具有统计学意义(P<0.05)。与正常组相比,模型1组与模型2组大鼠右后足垫软组织伊文思蓝(EB)露出量均明显增多(P<0.05),且模型1组与模型2组比较差异有统计学意义(P<0.05)。结论在CIA基础上结合风、湿、热环境刺激可以复制出符合中医证候特征的RA热痹证大鼠模型,且该模型起病及成模时间早、炎症程度更重;关节表面温度、热痛阈值和毛细血管通透性是该模型的特征性评价指标。

Objective To replicate and evaluate RA rat model of combination disease and syndrome accordance with the characteristics of heat arthralgia syndrome with heat,redness,swelling and pain in traditional Chinese medicine.Methods The 54 female wistar rats were randomly divided into 3 groups with 18 rats in each group,the normal group was fed,the model group 1 was stimulated with collagen-induced,and the model group 2 was stimulated by wind,wet and thermal environment on the basis of collagen induction.The model was evaluated with AI,joint surface temperature,thermal pain threshold and capillary permeability.Results The onset time of rats in model 2 were earlier than that in model 1 group(P<0.05),but there was no significant difference in modular rate between model 2 group(83%)and model 1 group(78%).The AI scores of model 1 group on the 28 th day and model 2 group on the 21 th and 28 th days were higher than 4,which indicated that the two groups of models were duplicated successfully.In model 2 and model 1,abnormal high temperature zone appeared on the surface of bilateral joints,and the temperature increased significantly(P<0.05),the surface temperature of bilateral joint in model group 2 was significantly higher than that in model group 1 on the 14 th,21 th and 28 th days(P<0.05).Compared with the normal group,the threshold of thermal pain in model 1 group was significantly lower than that in model 1 group at 21 th and 28 th days,and in model 2 group on the 14 th,21 th and 28 days,but difference of thermal pain threshold between model 2 group and model 1 group was statistically significant only on the 21 th day.Compared with the normal group,the EB exposure of the right hind foot pad and soft tissue in the two model group increased significantly(P<0.05),there was significant difference between model 1 group and model 2 group(P<0.05).Conclusion Combined with wind,wet and heat environment stimulation on the basis of CIA,the rat model of RA heat arthralgia syndrome which accords with the characteristics of TCM syndrome can be replicated,the onset and formation time of the model were early,and the degree of inflammation was more serious.Joint surface temperature,thermal pain threshold and capillary permeability were the characteristic indexes of the model.