【摘要】：目的研究束縛應(yīng)激對大鼠下丘腦腦源性神經(jīng)營養(yǎng)因子(brain derived neurotrophic factor,BDNF)和生長相關(guān)蛋白(growth associated protein 43,GAP-43)表達(dá)的影響,并分析BDNF和GAP-43在慢性應(yīng)激致類抑郁樣癥狀發(fā)生中的作用以及CP-154526的治療作用。方法將30只雄性SD大鼠隨機(jī)分成3組,即束縛應(yīng)激組、CP-154526治療組和對照組。束縛應(yīng)激組采用每日束縛3 h、連續(xù)21 d的方法建立抑郁癥模型,促腎上腺皮質(zhì)激素釋放激素1受體(corticotrophin-releasing hormone type 1receptor,CRH1R)阻斷劑CP-154526治療組自實(shí)驗(yàn)開始用CP-154526對抑郁模型動物予以治療,對照組注射CP-154526的溶劑DMSO。觀測各組大鼠行為學(xué)變化;酶聯(lián)免疫吸附實(shí)驗(yàn)檢測血漿促腎上腺皮質(zhì)激素釋放激素(corticotropin releasing hormonecorti,CRH)濃度;Western blot檢測模型大鼠下丘腦BDNF、GAP-43蛋白表達(dá)表達(dá)情況。結(jié)果束縛應(yīng)激組與對照組和治療組相比體質(zhì)量增長下降(P0.05)、和糖水偏好率均顯著下降(P0.05),在穿格次數(shù)、站立次數(shù)、修飾次數(shù)均少于對照組(P0.05);而治療組與對照組以上實(shí)驗(yàn)結(jié)果無統(tǒng)計(jì)學(xué)差異(P0.05)。束縛應(yīng)激組血漿CRH濃度較對照組升高(P0.05),但治療組血漿CRH濃度較對照組無統(tǒng)計(jì)學(xué)差異(P0.05)。束縛應(yīng)激組下丘腦BDNF、GAP-43表達(dá)較對照組與治療組增多(P0.05)。結(jié)論慢性束縛應(yīng)激可致大鼠下丘腦BDNF、GAP-43蛋白表達(dá)上調(diào),導(dǎo)致下丘腦發(fā)生可塑性變化,與下丘腦CRH分泌增多以及抑郁癥行為的變化相關(guān)。CRH1R阻斷劑CP-154526可逆轉(zhuǎn)下丘腦BDNF和GAP-43蛋白的表達(dá),改善類抑郁癥狀。
[Abstract]:Objective to study the effects of restraint stress on the expression of brain-derived neurotrophic factor (brain derived neurotrophic factor,BDNF) and growth-associated protein (growth associated protein 43) in rat hypothalamus. The role of BDNF and GAP-43 in the development of depression-like symptoms induced by chronic stress and the therapeutic effect of CP-154526 were analyzed. Methods Thirty male SD rats were randomly divided into three groups: restraint stress group, CP-154526 treatment group and control group. The depression model was established in the restraint stress group by 3 hours per day for 21 days, and the adrenocorticotropic hormone releasing hormone 1 receptor (corticotrophin-releasing hormone type 1 receptor) was used to establish the depression model. CRH1R) CP-154526 treatment group has been treated with CP-154526 since the experiment, and the control group has been injected with DMSO., the solvent of CP-154526. The changes of behavior and the expression of BDNF,GAP-43 protein in hypothalamus of model rats were detected by enzyme linked immunosorbent assay (Elisa) and plasma corticotropin releasing hormone (corticotropin releasing hormonecorti,CRH) concentration; Western blot. Results compared with the control group and the treatment group, the growth of body mass in the restraint stress group decreased (P0.05), and the preference rate of sugar water decreased significantly (P0.05), and the number of piercing, standing and modification in the control group was lower than that in the control group (P0.05). But the treatment group and the control group above experiment result has no statistical difference (P0.05). The plasma CRH concentration in the restraint stress group was higher than that in the control group (P0.05), but the plasma CRH concentration in the treatment group was not significantly different from that in the control group (P0.05). The expression of BDNF,GAP-43 in hypothalamus in restraint stress group was higher than that in control group and treatment group (P0.05). Conclusion chronic restraint stress can increase the expression of BDNF,GAP-43 protein in hypothalamus and induce plasticity of hypothalamus. CP-154526 can reverse the expression of BDNF and GAP-43 protein in hypothalamus and ameliorate depressive symptoms.
【作者單位】： 第三軍醫(yī)大學(xué)大坪醫(yī)院野戰(zhàn)外科研究所老年科;第三軍醫(yī)大學(xué)大坪醫(yī)院野戰(zhàn)外科研究所神經(jīng)外科;
【基金】：重慶市自然科學(xué)基金(cstc2013jj B10002)~~
【分類號】：R965

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