CAJ | 학술논문

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。
위료연구만성응격성억욱발생중해마전화생장인자β1（transforming growth factor beta ！1， TGF-β1）화서단백 P 적작용급기관계，실험통과건립만성불가예견성온화응격（Chronic Unpredictable Mild Stress ，CUMS）동물억욱모형，동시해마내미량주사 TGF-β1이급 TGF-β1형수체격매억제제 LY-364947，연후측량대서체중변화솔，병통과당수소모이급광장실험、현미실험검측대서행위변화，운용Elisa、Western blot분별검측대서해마조직내TGF-β1화서단백P적함량변화。결과현시，여정상대조조상비，CUMS조대서표현출명현적억욱양행위，해마조직내 TGF-β1함량승고，서단백P표체하강；정상대서해마내주사 TGF-β1병불도치억욱양행위，상반，CUMS동시해마내주사TGF-β1능역전응격도치적억욱양행위；정상화 CUMS대서해마주사 TGF-β1균능명현억제서단백P적표체；이응격적동시주사 TGF-β1형수체격매억제제 LY-364947동양구유항억욱효응，차시서단백P표체교CUMS조명현승고。이상결과표명：해마TGF-β1화서단백P삼여료응격성억욱적발생；서단백P대해마가능구유보호작용，TGF-β1통과 TGF-β1형수체억제서단백P표체가능시도치억욱발생적도경지일，이 TGF-β1항억욱작용가능시경과 TGF-β1형수체이외적기타도경실현。
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.