CAJ | 학술논문

目的：研究氟西汀对慢性应激大鼠前额叶谷氨酸转运体1(GLT-1)的影响,进一步探讨氟西汀抗抑郁作用可能的分子机制。方法正常SD大鼠60只,随机分为对照组、慢性不可预见性应激( CUS)组和氟西汀组。对CUS组和氟西汀组大鼠进行CUS应激后,氟西汀组给予氟西汀治疗,对照组和CUS组给予生理盐水。实验结束后进行糖水偏好和旷场行为测试,并使用免疫组织化学法和蛋白印迹分析检测大鼠前额叶GLT-1的表达水平。结果(1)行为学测试结果显示,CUS组大鼠糖水偏好、总行程、平均移动速度及直立次数均低于对照组(P<0．01)；氟西汀组上述指标均高于CUS组(P<0．01)。(2)免疫组织化学法分析显示,CUS组与对照组比较,大鼠前额叶GLT-1表达下降( P<0．01)；经氟西汀治疗后,大鼠前额叶GLT-1表达比CUS组明显升高( P<0．01)。(3)蛋白印迹分析显示,CUS组与对照组比较,大鼠前额叶GLT-1表达下降( P<0．01)；经氟西汀治疗后,大鼠前额叶GLT-1表达比CUS明显升高( P<0．01)。结论慢性应激下调大鼠前额叶 GLT-1表达水平,而氟西汀上调GLT-1表达水平,GLT-1表达增加可能是氟西汀抗抑郁作用的分子机制之一。
목적：연구불서정대만성응격대서전액협곡안산전운체1(GLT-1)적영향,진일보탐토불서정항억욱작용가능적분자궤제。방법정상SD대서60지,수궤분위대조조、만성불가예견성응격( CUS)조화불서정조。대CUS조화불서정조대서진행CUS응격후,불서정조급여불서정치료,대조조화CUS조급여생리염수。실험결속후진행당수편호화광장행위측시,병사용면역조직화학법화단백인적분석검측대서전액협GLT-1적표체수평。결과(1)행위학측시결과현시,CUS조대서당수편호、총행정、평균이동속도급직립차수균저우대조조(P<0．01)；불서정조상술지표균고우CUS조(P<0．01)。(2)면역조직화학법분석현시,CUS조여대조조비교,대서전액협GLT-1표체하강( P<0．01)；경불서정치료후,대서전액협GLT-1표체비CUS조명현승고( P<0．01)。(3)단백인적분석현시,CUS조여대조조비교,대서전액협GLT-1표체하강( P<0．01)；경불서정치료후,대서전액협GLT-1표체비CUS명현승고( P<0．01)。결론만성응격하조대서전액협 GLT-1표체수평,이불서정상조GLT-1표체수평,GLT-1표체증가가능시불서정항억욱작용적분자궤제지일。
Aim To investigate the effects of fluoxe-tine on the changes of of protein levels of GLT-1 in pre-frontal cortex in rat depression model, and to further explore the molecular mechanism of antidepressant ac-tion of fluoxetine. Methods Sixty male SD rats were randomly assigned into three groups: control group, chronic unpredictable stress ( CUS) group, and CUS+fluoxetine group. The rats of CUS group and CUS+flu-oxetine group were subjected to CUS for 2 sessions per day for 35 days. Then, the rats of the CUS+fluoxetine group were given fluoxetine for 28 days. Behavioral changes were assessed by the sucrose preference and open field tests. The GLT-1 protein levels in the pre-frontal cortex were detected by immunohistochemistry and Western blot analysis at the end of the fluoxetine treatment. Results ( 1 ) Compared with the control group,sucrose preference, total traveling distance, ve-locity and frequencies of rearing were reduced in the CUS group ( P < 0. 01 ) . These behavioral changes could be reversed after 28 day fluoxetine treatment. (2 ) Immunohistochemistry assay indicated weak im-munoreactivity for GLT-1 in the prefrontal cortex of CUS group ( versus the control rats: P <0. 01 ); the immunoreactivity for GLT-1 of the fluoxetine-treated rats was significantly up-regulated compared with the CUS group rats ( P<0. 01 ) . ( 3 ) Western blot analy-sis indicated significant reductions of GLT-1 in the pre-frontal cortex of CUS group ( versus the control rats:P<0. 01 ) , and chronic fluoxetine treatment reversed the CUS-induced decrease in GLT-1 levels ( P <0. 01 ) . Conclusions Chronic unpredictable stress ( CUS ) could down-regulate the GLT-1 protein levels in the prefrontal cortex, which is reversed by fluoxe-tine. These results further support the notion that en-hanced expression of the GLT-1 protein could be mo-lecular mechanism of fluoxetine antidepressant effect.