转化生长因子-β1与硒蛋白P在慢性应激性抑郁发生中的作用及关系  

Involvement of transforming growth factor beta-1 and selenoprotein P in depression induced by chronic stress

作　　者：李菲[1] 陈慧彬[1] 吴帅[1] 安书成[1] 

机构地区：[1]陕西师范大学生命科学学院,陕西西安710119

出　　处：《陕西师范大学学报（自然科学版）》2014年第4期57-64,共8页Journal of Shaanxi Normal University：Natural Science Edition

基　　金：国家自然科学基金资助项目(81271488);中央高校基本科研业务费专项资金项目(GK200901011)

摘　　要：为了研究慢性应激性抑郁发生中海马转化生长因子β1(transforming growth factor beta–1,TGF-β1)和硒蛋白P的作用及其关系,实验通过建立慢性不可预见性温和应激(Chronic Unpredictable Mild Stress,CUMS)动物抑郁模型,同时海马内微量注射TGF-β1以及TGF-β1型受体激酶抑制剂LY-364947,然后测量大鼠体重变化率,并通过糖水消耗以及旷场实验、悬尾实验检测大鼠行为变化,运用Elisa、Western blot分别检测大鼠海马组织内TGF-β1和硒蛋白P的含量变化.结果显示,与正常对照组相比,CUMS组大鼠表现出明显的抑郁样行为,海马组织内TGF-β1含量升高,硒蛋白P表达下降;正常大鼠海马内注射TGF-β1并不导致抑郁样行为,相反,CUMS同时海马内注射TGF-β1能逆转应激导致的抑郁样行为;正常和CUMS大鼠海马注射TGF-β1均能明显抑制硒蛋白P的表达;而应激的同时注射TGF-β1型受体激酶抑制剂LY-364947同样具有抗抑郁效应,此时硒蛋白P表达较CUMS组明显升高.以上结果表明:海马TGF-β1和硒蛋白P参与了应激性抑郁的发生;硒蛋白P对海马可能具有保护作用,TGF-β1通过TGF-β1型受体抑制硒蛋白P表达可能是导致抑郁发生的途径之一,而TGF-β1抗抑郁作用可能是经过TGF-β1型受体以外的其他途径实现.In order to investigate the role and relationship between transforming growth factor-beta1 （TGF-β1 ）and selenoprotein P in depression induced by chronic unpredictable mild stress （CUMS）,the effects of intrahippocampal microinjections of TGF-β1 and its receptor kinase inhibitor （LY-364947 ） on CUMS-induced depression and anxiety-like behaviors were investigated.The levels of depression like behaviors and related properties were measured using open-field test,tail suspension test,sucrose consumption and the body weight.The content level of TGF-β1 and the selenoprotein P were detected by Elisa and Western blot respectively.The results show that compared with control group,CUMS rats showed significant depression-like behaviors,lower levels of selenoprotein P and higher levels of TGF-β1 in the hippocampus.Microinj ection of recombined TGF-β1 didn′t result in increase of depressive-like behaviors;however,intrahippocampal inj ection of recombined TGF-β1 can effectively reduced the depressive-like behaviors induced by CUMS.TGF-β1 inhibited the expression of selenoprotein P.Interestingly, microinj ection of LY-3 6 4 9 4 7 ,the inhibitor of TGF-beta type 1 receptor kinase into hippocampus also showed anti-depression effect and the expression of selenoprotein P was higher compared with CUMS/SAL group.These data suggest that selenoprotein P and TGF-β1 in the hippocampus are involved in chronic stress induced depression.Selenoprotein P may play a role in the protection of hippocampus.It may be involved in the occurrence of depression in which TGF-β1 inhibits the expression of selenoprotein P via TGF-beta type 1 receptor .The antidepressant effects of TGF-beta 1 may be via other ways without the TGF-beta type 1 receptor.

关 键 词：应激 抑郁 转化生长因子-Β1 硒蛋白P 

分 类 号：Q189[生物学—神经生物学]