中药益肾平肝方对脱髓鞘模型小鼠社会交互行为的影响及作用靶点

Effects of Yishenpingganfang, an empirical prescription on social interaction behavior in mice exposed to cuprizone and its possible action target

目的观察中药益肾平肝方对精神分裂症的治疗效果以及探究其作用的潜在靶标。方法实验动物采用成年雄性C57BL/6小鼠,6周龄,实验分为3组,每组10只:对照组,cuprizone(CPZ)模型组和益肾平肝方(Yishenpingganfang,YSPGF)治疗组,实验共进行6周。社会交互实验以及组织采集在最后一次给予中药治疗24h后进行。采用社会交互实验以评价YSPGF对小鼠精神分裂症样行为的影响;采用髓鞘特异性免疫组化和Western blotting观察成熟少突胶质细胞及少突胶质细胞前体细胞的表达变化。结果 CPZ模型组小鼠于第3周出现明显体质量下降(P <0. 05),YSPGF治疗组与CPZ模型组相比,体质量差异无统计学意义(P>0. 05);社会交互实验:Trial 1实验中:对照组小鼠围绕陌生小鼠1 (Stranger 1)的时间明显大于围绕空杯子(Empty)的时间(P <0. 001)。YSPGF组与对照组类似,围绕Stranger 1与Empty的时间差异有统计学意义(P <0. 01)。但模型组小鼠围绕Stranger 1与Empty的时间之间差异无统计学意义(P>0. 05)。Trial 2实验中:对照组小鼠对新加入的Stranger 2较之已经熟悉的Stranger 1更加感兴趣(P <0. 001)第;成熟少突胶质细胞特异性抗体髓鞘碱性蛋白(myelin basic protein,MBP)免疫组织化学染色和Western blotting显示:CPZ模型组小鼠成熟胶质细胞/髓鞘在胼胝体有一定程度缺失,YSPGF组与CPZ模型组相比,髓鞘脱失有所好转。进一步实验显示:少突胶质细胞前体细胞血小板源生长因子受体α(platelet-derived growth factor receptoralpha,PDGFR-α)在CPZ诱导脱髓鞘后有反应性增生。结论中药YSPGF可以改善CPZ诱导小鼠的社会退缩,改善少突胶质细胞/髓鞘结构的损害。

Objective To explore the effect and potential target of Yishenpingganfang(YSPGF)in schizophrenia treatment.Methods Totally 30 Young adult male C57 BL/6 mice(6 weeks old)were randomly divided into three groups:normal control,cuprizone(CPZ)model,and YSPGF group.This study lasts for 6 weeks.Then,social interaction tests and brain tissue collections were carried out 24 h later after 2-week period of drug admission.Social interaction was used to evaluate schizophrenia-like symptoms in mice exposed to cuprizone and partly treated by YSPGF.The mature oligodendrocyte/myelin deficiency and immature oligodendrocyte changes were observed with histological staining.Results The body weight in the model group were obviously decreased in week 3 compared with the control group(P<0.05).Social interaction included two trials:In trial 1,control mice spent more time interacting with the stranger mouse than with the empty cage and familiar one(P<0.001)as well as YSPGF group(P<0.01).In trial 2,control mice preferred to be near the new stranger mouse than the familiar one(P<0.001).In contrast,CPZ mice showed no preference between the empty cage and the stranger mouse in both trials 1 and 2.The oligodendrocyte/myelin deficiency existed in callosum through using mature oligodendrocyte maker myelin basic protein(MBP).Furthermore,we used immature oligodendrocyte maker platelet-derived growth factor receptor-alpha(PDGFR-α)and found that in model group mice these immature oligodendrocyte increased after the demyelination stage.Conclusion YSPGF could improve CPZ-induced psychosis-like behaviors and reduce oligodendrocyte/myelin deficiency.