基于胶质细胞增殖调控因子bFGF/TGF-β1探讨逍遥散治疗抑郁症的机制

Mechanism of the treatment of depression with Xiaoyao Powder based on glial cell proliferation regulator bFGF/TGF-β1

目的基于胶质细胞增殖调控因子bFGF/TGF-β1探讨逍遥散治疗抑郁症的机制。方法采用CUMS方法建立抑郁症小鼠模型。造模成功后,给予逍遥散和盐酸氟西汀干预,对小鼠体重、摄食量、行为学进行评估;采用Elisa、免疫组化和Western blotting方法检测小鼠前额皮质bFGF和TGF-β1蛋白表达情况及逍遥散的调节作用。结果模型组小鼠体重、饮食情况、糖水摄入量较正常组小鼠出现显著降低(P<0.01),强迫游泳不动时间显著延长(P<0.01),经逍遥散和氟西汀治疗以后得到显著改善(P<0.05);另外Elisa、免疫组化和western blot实验结果均表明,抑郁症小鼠前额皮质bFGF蛋白含量表达显著降低(P<0.01),经逍遥散和氟西汀治疗后,抑郁症小鼠前额皮质bFGF蛋白表达情况可被扭转(P<0.05),而各组小鼠前额皮质TGF-β1蛋白表达情况与bFGF刚好相反。结论逍遥散可通过调控AST抑制剂TGF-β1和促活化剂bFGF而发挥治疗抑郁症的作用,其机制可能与逍遥散通过bFGF/TGF-β1调控前额皮质AST功能有关。

Objective To explore the mechanism of Xiaoyao Powder in treating depression based on glial cell proliferation regulator bFGF/TGF-β1.Methods A mouse model of depression was established using a chronic unpredictable mild stress method.After successful modeling,Xiaoyao Powder and fluoxetine hydrochloride were given to evaluate the body weight,food intake and behavior.Elisa,immunohistochemistry and Western blotting were used to detect the expression of bFGF and TGF-β1 proteins in prefrontal cortex of mice and the regulatory effects of Xiaoyao Powder.Results Compared with the normal group,the body weight,food intake,and syrup preference of the model group decreased significantly(P<0.01),forced swimming immobility time was significantly prolonged(P<0.01),and significantly improved after treatment with Xiaoyao Powder and fluoxetine(P<0.05).In addition,the results of Elisa,immunohistochemistry and western blot showed that the content and expression of bFGF protein in the prefrontal cortex of the model group were significantly decreased(P<0.01),Xiaoyao Powder and fluoxetine treatment can significantly reverse the expression of bFGF protein in prefrontal cortex of depressed mice(P<0.05).However,the expression of TGF-β1 protein in the prefrontal cortex of each group was just the opposite of bFGF.Conclusion Xiaoyao Powder can play a role in the treatment of depression by regulating AST inhibitor TGF-β1 and activator bFGF.The mechanism may be related to Xiaoyao Powder’s regulation of prefrontal cortex AST function through bFGF/TGF-β1.