国际脑血管病杂志
國際腦血管病雜誌
국제뇌혈관병잡지
INTERNATIONAL JOURNAL OF CEREBROVASCULAR DISEASES
2014年
3期
182-187
,共6页
卒中%脑缺血%抑郁症%西酞普兰%白细胞介素-18%疾病模型,动物%大鼠
卒中%腦缺血%抑鬱癥%西酞普蘭%白細胞介素-18%疾病模型,動物%大鼠
졸중%뇌결혈%억욱증%서태보란%백세포개소-18%질병모형,동물%대서
Stroke%Brain Ischemia%Depression%Interleukin-18%Citalopram%Disease Models,Animal%Rats
目的 探讨艾司西酞普兰对卒中后抑郁(post-stroke depression,PSD)模型大鼠血清促炎细胞因子白细胞介素-6(Interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和IL-18水平的影响.方法 24只雄性Sprague-Dawley大鼠随机分为假手术组、大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)组、PSD组和艾司西酞普兰组,每组6只.采用线栓法建立大鼠大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型,并在此基础上结合慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)加孤养建立PSD模型.假手术组和MCAO组不CUMS也不孤养,PSD组CUMS并孤养,艾司西酞普兰组在开始CUMS和孤养时给予艾司西酞普兰干预[10 mg/(kg·d),腹腔注射,共3周].在基线以及CUMS后7、14和21 d利用蔗糖溶液消耗和旷野试验进行抑郁样行为学评估.应用酶联免疫吸附法检测CUMS后22 d时血清促炎细胞因子IL-6、TNF-α和IL-18水平.结果 CUMS后21 d时,PSD组体重、蔗糖溶液消耗、垂直运动得分和水平运动距离均较假手术组和MCAO组显著性降低和缩短(P均＜0.01),艾司西酞普兰组体重、蔗糖溶液消耗和水平运动距离均较PSD组显著性增加(P＜0.05或P＜0.01).CUMS后22 d时,PSD组血清IL-18水平较假手术组和MCAO组显著性升高(P＜0.05或P＜0.01),艾司西酞普兰组血清IL-18水平较PSD组显著性降低(P＜0.05),但各组间IL-6和TNF-α水平均无显著性差异.相关分析显示,CUMS后22 d时,血清IL-18水平与蔗糖溶液消耗(r=-0.415,P=0.044)、旷野试验中水平运动距离(r=-0.508,P=0.011)均呈显著负相关,但与垂直运动得分(r=-0.390,P=0.059)和体重无显著相关性(r=-0.216,P=0.311).结论 PSD模型大鼠血清IL-18水平显著性升高,艾司西酞普兰能显著性降低PSD大鼠血清IL-18水平并改善抑郁样行为,提示IL-18可能在PSD的发病机制中起一定的作用.
目的 探討艾司西酞普蘭對卒中後抑鬱(post-stroke depression,PSD)模型大鼠血清促炎細胞因子白細胞介素-6(Interleukin-6,IL-6)、腫瘤壞死因子-α(tumor necrosis factor-α,TNF-α)和IL-18水平的影響.方法 24隻雄性Sprague-Dawley大鼠隨機分為假手術組、大腦中動脈閉塞(middle cerebral artery occlusion,MCAO)組、PSD組和艾司西酞普蘭組,每組6隻.採用線栓法建立大鼠大腦中動脈閉塞(middle cerebral artery occlusion,MCAO)模型,併在此基礎上結閤慢性不可預見性溫和應激(chronic unpredictable mild stress,CUMS)加孤養建立PSD模型.假手術組和MCAO組不CUMS也不孤養,PSD組CUMS併孤養,艾司西酞普蘭組在開始CUMS和孤養時給予艾司西酞普蘭榦預[10 mg/(kg·d),腹腔註射,共3週].在基線以及CUMS後7、14和21 d利用蔗糖溶液消耗和曠野試驗進行抑鬱樣行為學評估.應用酶聯免疫吸附法檢測CUMS後22 d時血清促炎細胞因子IL-6、TNF-α和IL-18水平.結果 CUMS後21 d時,PSD組體重、蔗糖溶液消耗、垂直運動得分和水平運動距離均較假手術組和MCAO組顯著性降低和縮短(P均＜0.01),艾司西酞普蘭組體重、蔗糖溶液消耗和水平運動距離均較PSD組顯著性增加(P＜0.05或P＜0.01).CUMS後22 d時,PSD組血清IL-18水平較假手術組和MCAO組顯著性升高(P＜0.05或P＜0.01),艾司西酞普蘭組血清IL-18水平較PSD組顯著性降低(P＜0.05),但各組間IL-6和TNF-α水平均無顯著性差異.相關分析顯示,CUMS後22 d時,血清IL-18水平與蔗糖溶液消耗(r=-0.415,P=0.044)、曠野試驗中水平運動距離(r=-0.508,P=0.011)均呈顯著負相關,但與垂直運動得分(r=-0.390,P=0.059)和體重無顯著相關性(r=-0.216,P=0.311).結論 PSD模型大鼠血清IL-18水平顯著性升高,艾司西酞普蘭能顯著性降低PSD大鼠血清IL-18水平併改善抑鬱樣行為,提示IL-18可能在PSD的髮病機製中起一定的作用.
목적 탐토애사서태보란대졸중후억욱(post-stroke depression,PSD)모형대서혈청촉염세포인자백세포개소-6(Interleukin-6,IL-6)、종류배사인자-α(tumor necrosis factor-α,TNF-α)화IL-18수평적영향.방법 24지웅성Sprague-Dawley대서수궤분위가수술조、대뇌중동맥폐새(middle cerebral artery occlusion,MCAO)조、PSD조화애사서태보란조,매조6지.채용선전법건립대서대뇌중동맥폐새(middle cerebral artery occlusion,MCAO)모형,병재차기출상결합만성불가예견성온화응격(chronic unpredictable mild stress,CUMS)가고양건립PSD모형.가수술조화MCAO조불CUMS야불고양,PSD조CUMS병고양,애사서태보란조재개시CUMS화고양시급여애사서태보란간예[10 mg/(kg·d),복강주사,공3주].재기선이급CUMS후7、14화21 d이용자당용액소모화광야시험진행억욱양행위학평고.응용매련면역흡부법검측CUMS후22 d시혈청촉염세포인자IL-6、TNF-α화IL-18수평.결과 CUMS후21 d시,PSD조체중、자당용액소모、수직운동득분화수평운동거리균교가수술조화MCAO조현저성강저화축단(P균＜0.01),애사서태보란조체중、자당용액소모화수평운동거리균교PSD조현저성증가(P＜0.05혹P＜0.01).CUMS후22 d시,PSD조혈청IL-18수평교가수술조화MCAO조현저성승고(P＜0.05혹P＜0.01),애사서태보란조혈청IL-18수평교PSD조현저성강저(P＜0.05),단각조간IL-6화TNF-α수평균무현저성차이.상관분석현시,CUMS후22 d시,혈청IL-18수평여자당용액소모(r=-0.415,P=0.044)、광야시험중수평운동거리(r=-0.508,P=0.011)균정현저부상관,단여수직운동득분(r=-0.390,P=0.059)화체중무현저상관성(r=-0.216,P=0.311).결론 PSD모형대서혈청IL-18수평현저성승고,애사서태보란능현저성강저PSD대서혈청IL-18수평병개선억욱양행위,제시IL-18가능재PSD적발병궤제중기일정적작용.
Objective To investigate the effect of escitalopram on the levels of serum proinflammatory cytokine interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),and IL-18 in a rat model of poststroke depression (PSD).Methods Twenty-four male Sprague-Dawley rats were randomly allocated into sham operation,middle cerebral artery occlusion (MCAO),PSD and escitalopram groups (n =6 in each group).A model of MCAO was induced by the intraluminal suture method,and on this basis,a PSD model was induced by combining with chronic unpredictable mild stress (CUMS) plus lonely upbringing.The rats of both the sham operation group and the MCAO group were neither CUMS nor lonely upbringing,and in the PSD group they were both CUMS and lonely upbringing.The escitalopram group was given escitalopram intervention (10 mg/kg · d,intraperitoneal injection for 3 weeks) at the beginning of CUMS and lonely upbringing.At baseline and on day 7,14 and 21 after CUMS,sucrose solution consumption and wilderness trials were used to assess depression-like behavior.Enzyme-linked immunosorbent assay was used to detect the levels of serum proinflammatory cytokines IL-6,TNF-α and IL-18 on day 21 after CUMS.Results On day 21 after CUMS,the scores of weight,sucrose solution consumption,vertical test and the distance of horizontal activities were all significantly decreased and shortened compared to those of the sham operation group and the MCAO group (all P＜0.01).The weight,sucrose solution consumption,and the distance of horizontal activities of the escitalopram group were significantly increased compared to those of the PSD group (P ＜0.05 or P ＜0.01).On day 22 after CUMS,the serum IL-18 level of the PSD group was increased significantly compared to that of the sham operation group and the MCAO group (P ＜ 0.05 or P ＜ 0.01).The serum IL-18 level of the escitalopram group was decreased significantly compared to that of the PSD group (P ＜0.05).However,there were no significant differences in the levels of IL-6 and TNF-α among all the groups.Correlation analysis showed that on day 22 after CUMS,the serum IL-18 level and sucrose solution consumption (r =-0.415,P =0.044),the distance of horizontal activities in the wilderness trials (r =-0.508,P =0.011) showed a significant negative correlation,however,they did not have significant correlation with the vertical score (r =-0.390,P=0.059) and the body weight (r=-0.216,P=0.311).Conclusions The serum IL-18 level is increased significantly in the PSD rat models.Escitalopram can significantly decrease the serum IL-18 level and improve depression-like behavior of the PSD rats,suggesting that IL-18 may play a role in the pathogenesis of PSD.
