壮骨止痛解郁方对RAD模型大鼠行为学及FKN/CX3CR1信号通路的影响

Effects of Zhuanggu Zhitong Jieyu Formula on Behavioristics and FKN/CX3CR1 Signaling Pathway of RAD Model Rats

目的:探讨壮骨止痛解郁方对类风湿性关节炎伴发抑郁症(RAD)模型大鼠行为学和趋化因子Fractalkine(FKN)及其受体CX3CR1的影响。方法:40只SD大鼠随机分为空白组、模型组、西药组和中药组,除空白组外,其余各组采用Ⅱ型胶原蛋白-弗氏完全佐剂和慢性不可预知的应激加孤养建立RAD模型,应激造模的同时,西药组灌胃甲氨蝶呤和氟西汀,中药组灌胃壮骨止痛解郁方,模型组灌胃蒸馏水。给药28 d后,采用糖水偏好和旷场实验评价各组大鼠的行为学情况,ELISA法检测血清中TNF-α、FKN含量,免疫组化法观察脑内CX3CR1的阳性表达。结果:与空白组比较,模型组大鼠糖水偏好率和自主活动得分降低(P<0.01),血清TNF-α、FKN含量增加(P<0.01),脑内海马区域CX3CR1免疫阳性表达升高(P<0.01);与模型组比较,中药组大鼠糖水偏好率和自主活动得分升高(P<0.01),血清TNF-α、FKN含量减少(P<0.01),脑内CX3CR1免疫阳性表达降低(P<0.01)。结论:壮骨止痛解郁方能明显改善RAD模型大鼠的快感缺失和自主活动行为,其机制可能与调节FKN/CX3CR1信号通路的作用密切相关。

Objective:To investigate the effects of Zhuanggu Zhitong Jieyu Formula on behavioristics,chemokine Fractalkine(FKN)and its receptor CX3 CR1 of rats with rheumatoid arthritis accompanied by depression(RAD).Methods:40 SD rats were randomly divided into the blank group,the model group,the western medication group and the Chinese medication group.The RAD model was established by typeⅡcollagen-complete Freund’s adjuvant(CFA)emulsion combined with chronic unpredictable stress and solitary rearing.Meanwhile,the western medication group was treated with Methotrexate and Fluoxetine,whereas the Chinese medication group was treated with Zhuanggu Zhitong Jieyu Formula.The blank group and the model group were given distilled water.After 28 days of administration,the behavior of rats in each group was evaluated by the preference of sugar water and open-field test.The serum contents of TNF-αand FKN were tested by ELISA,and the positive expression of CX3 CR1 in brain was observed by immunohistochemistry assay.Results:Compared to those in the blank group,the preference rate of sugar water and the score of independent activity were significantly decreased(P<0.01),the serum contents of TNF-αand FKN were greatly increased(P<0.01),and the positive expression of CX3 CR1 in hippocampus was obviously enhanced in the model group(P<0.01).Compared to those in the model group,the preference rate of sugar water and the score of independent activity were significantly increased(P<0.01),the serum contents of TNF-αand FKN were greatly decreased(P<0.01),and the positive expression of CX3 CR1 in hippocampus was obviously lowered in the Chinese medication group(P<0.01).Conclusion:Zhuanggu Zhitong Jieyu Formula can significantly improve the lack of pleasure and the independent activity of RAD model rats,which mechanism may be closely related to the regulation of FKN/CX3 CR1 signaling pathway.