中国卒中杂志
中國卒中雜誌
중국졸중잡지
CHINESE JOURNAL OF STROKE
2014年
12期
999-1006
,共8页
李海龙%刘敏%张海%郑惠文%周凯歌%王云霞%毕晓莹
李海龍%劉敏%張海%鄭惠文%週凱歌%王雲霞%畢曉瑩
리해룡%류민%장해%정혜문%주개가%왕운하%필효형
血管性抑郁%炎症因子%神经递质%抗炎治疗
血管性抑鬱%炎癥因子%神經遞質%抗炎治療
혈관성억욱%염증인자%신경체질%항염치료
Vascular depression%Inflammatory cytokines%Neurotransmitters%Anti-inlfammatory treatment
目的探讨minocycline抑制炎症反应对血管性抑郁小鼠行为及神经递质的影响。<br> 方法成年雄性CD1小鼠随机分为3组，每组各10只，实验组造模后立即腹腔注射minocycline每日1次连续7 d（30 mg/kg），对照组造模后给予同等剂量的生理盐水，假手术组除不阻断颈动脉供血外，其余手术操作与实验组相同，术后同样给予腹腔注射相应剂量的生理盐水。术后第8天起行悬尾实验（第8天）、旷场实验（第9天）检测抑郁行为，水迷宫定向航行实验（第10天）检测认知能力。术后第11天处死取脑，分离海马匀浆，酶联免疫吸附测定（enzyme-linked immunosorbent assay，ELISA）试剂盒检测肿瘤坏死因子-α（tumor necrosis factor α，TNF-α）、白细胞介素-1β（interleukin-1β，IL-1β）及白细胞介素-6（interleukin-6，IL-6）含量，并通过高效液相色谱法（high performance liquid chromatography，HPLC）对抑郁相关的单胺类神经递质进行检测，包括5-羟色胺（5-hydroxytryptamine，5-HT）、去甲肾上腺素（norepinephrine，NE）及多巴胺（dopamine，DA）。<br> 结果3组小鼠悬尾实验不动时间差异有显著性[实验组：（174.75±11.37）s，对照组：（194.32±14.32）s，假手术组：（169.62±19.27）s，F=6.59，P=0.005]；与对照组相比，实验组和假手术组悬尾不动时间显著缩短；3组小鼠探洞次数、活动时间、活动路程差异显著（F=6.17，P=0.008；F=11.55，P＜0.001；F=13.47，P＜0.001）；与对照组相比，实验组与假手术组探洞次数明显增多[实验组：（50.86±9.23）次，对照组：（35.73±11.96）次，假手术组：（48.14±10.16）次]，活动时间与活动总路程均明显延长[实验组：（786.70±27.51）s，对照组：（738.88±36.00）s，假手术组：（807.90±33.16）s；实验组：（37171.42±8493.40）mm，对照组：（28992.91±5760.03）mm，假手术组：（47206.23±8219.84）mm]；水迷宫实验潜伏期差异有显著性[实验组：（87.38±13.36）s，对照组：（88.50±19.88）s，假手术组：（44.38±19.76）s，F=16.09，P＜0.001]，与假手术组相比，实验组和对照组潜伏期显著延长。炎症因子检测提示，3组海马TNF-α、IL-1β及IL-6差异具有显著性[实验组：（141.10±24.36）pg/100 mg，对照组：（167.6±15.91）pg/100 mg，假手术组：（123.8±15.53） pg/100 mg，F=13.42，P＜0.001；实验组：（5.32±1.89）pg/mg，对照组：（10.31±2.83）pg/mg，假手术组：（4.50±2.07）pg/mg，F=18.69，P＜0.001；实验组：（20.01±3.62）pg/mg，对照组：（24.39±5.04）pg/mg，假手术组：（18.40±3.78）pg/mg，F=5.49，P=0.010]；与对照组相比，实验组与假手术组3种炎性细胞因子均显著降低。3组海马5-HT及DA含量差异有显著[实验组：（3.89±1.21）ng/ml，对照组：（3.13±1.44）ng/ml，假手术组：（5.01±1.68）ng/ml，F=4.17，P=0.026；实验组：（10.72±2.65）ng/ml，对照组：（7.99±2.31）ng/ml，假手术组：（11.76±3.10）ng/ml，F=5.18，P=0.012]；与对照组相比，实验组和假手术组DA含量显著增加，实验组5-HT含量差异无显著性，而假手术组5-HT含量增多；3组NE含量差异无显著性[实验组：（3.97±1.35）ng/ml，对照组：（3.16±1.55）ng/ml，假手术组：（4.68±1.99）ng/ml，F=2.13，P=0.139]。<br> 结论 Minocycline能够抑制血管性抑郁小鼠炎症因子的表达，抗炎症治疗可改善其抑郁行为，对认知损害未观察到明显改善，相关的神经递质以DA的改变为最明显。
目的探討minocycline抑製炎癥反應對血管性抑鬱小鼠行為及神經遞質的影響。<br> 方法成年雄性CD1小鼠隨機分為3組，每組各10隻，實驗組造模後立即腹腔註射minocycline每日1次連續7 d（30 mg/kg），對照組造模後給予同等劑量的生理鹽水，假手術組除不阻斷頸動脈供血外，其餘手術操作與實驗組相同，術後同樣給予腹腔註射相應劑量的生理鹽水。術後第8天起行懸尾實驗（第8天）、曠場實驗（第9天）檢測抑鬱行為，水迷宮定嚮航行實驗（第10天）檢測認知能力。術後第11天處死取腦，分離海馬勻漿，酶聯免疫吸附測定（enzyme-linked immunosorbent assay，ELISA）試劑盒檢測腫瘤壞死因子-α（tumor necrosis factor α，TNF-α）、白細胞介素-1β（interleukin-1β，IL-1β）及白細胞介素-6（interleukin-6，IL-6）含量，併通過高效液相色譜法（high performance liquid chromatography，HPLC）對抑鬱相關的單胺類神經遞質進行檢測，包括5-羥色胺（5-hydroxytryptamine，5-HT）、去甲腎上腺素（norepinephrine，NE）及多巴胺（dopamine，DA）。<br> 結果3組小鼠懸尾實驗不動時間差異有顯著性[實驗組：（174.75±11.37）s，對照組：（194.32±14.32）s，假手術組：（169.62±19.27）s，F=6.59，P=0.005]；與對照組相比，實驗組和假手術組懸尾不動時間顯著縮短；3組小鼠探洞次數、活動時間、活動路程差異顯著（F=6.17，P=0.008；F=11.55，P＜0.001；F=13.47，P＜0.001）；與對照組相比，實驗組與假手術組探洞次數明顯增多[實驗組：（50.86±9.23）次，對照組：（35.73±11.96）次，假手術組：（48.14±10.16）次]，活動時間與活動總路程均明顯延長[實驗組：（786.70±27.51）s，對照組：（738.88±36.00）s，假手術組：（807.90±33.16）s；實驗組：（37171.42±8493.40）mm，對照組：（28992.91±5760.03）mm，假手術組：（47206.23±8219.84）mm]；水迷宮實驗潛伏期差異有顯著性[實驗組：（87.38±13.36）s，對照組：（88.50±19.88）s，假手術組：（44.38±19.76）s，F=16.09，P＜0.001]，與假手術組相比，實驗組和對照組潛伏期顯著延長。炎癥因子檢測提示，3組海馬TNF-α、IL-1β及IL-6差異具有顯著性[實驗組：（141.10±24.36）pg/100 mg，對照組：（167.6±15.91）pg/100 mg，假手術組：（123.8±15.53） pg/100 mg，F=13.42，P＜0.001；實驗組：（5.32±1.89）pg/mg，對照組：（10.31±2.83）pg/mg，假手術組：（4.50±2.07）pg/mg，F=18.69，P＜0.001；實驗組：（20.01±3.62）pg/mg，對照組：（24.39±5.04）pg/mg，假手術組：（18.40±3.78）pg/mg，F=5.49，P=0.010]；與對照組相比，實驗組與假手術組3種炎性細胞因子均顯著降低。3組海馬5-HT及DA含量差異有顯著[實驗組：（3.89±1.21）ng/ml，對照組：（3.13±1.44）ng/ml，假手術組：（5.01±1.68）ng/ml，F=4.17，P=0.026；實驗組：（10.72±2.65）ng/ml，對照組：（7.99±2.31）ng/ml，假手術組：（11.76±3.10）ng/ml，F=5.18，P=0.012]；與對照組相比，實驗組和假手術組DA含量顯著增加，實驗組5-HT含量差異無顯著性，而假手術組5-HT含量增多；3組NE含量差異無顯著性[實驗組：（3.97±1.35）ng/ml，對照組：（3.16±1.55）ng/ml，假手術組：（4.68±1.99）ng/ml，F=2.13，P=0.139]。<br> 結論 Minocycline能夠抑製血管性抑鬱小鼠炎癥因子的錶達，抗炎癥治療可改善其抑鬱行為，對認知損害未觀察到明顯改善，相關的神經遞質以DA的改變為最明顯。
목적탐토minocycline억제염증반응대혈관성억욱소서행위급신경체질적영향。<br> 방법성년웅성CD1소서수궤분위3조，매조각10지，실험조조모후립즉복강주사minocycline매일1차련속7 d（30 mg/kg），대조조조모후급여동등제량적생리염수，가수술조제불조단경동맥공혈외，기여수술조작여실험조상동，술후동양급여복강주사상응제량적생리염수。술후제8천기행현미실험（제8천）、광장실험（제9천）검측억욱행위，수미궁정향항행실험（제10천）검측인지능력。술후제11천처사취뇌，분리해마균장，매련면역흡부측정（enzyme-linked immunosorbent assay，ELISA）시제합검측종류배사인자-α（tumor necrosis factor α，TNF-α）、백세포개소-1β（interleukin-1β，IL-1β）급백세포개소-6（interleukin-6，IL-6）함량，병통과고효액상색보법（high performance liquid chromatography，HPLC）대억욱상관적단알류신경체질진행검측，포괄5-간색알（5-hydroxytryptamine，5-HT）、거갑신상선소（norepinephrine，NE）급다파알（dopamine，DA）。<br> 결과3조소서현미실험불동시간차이유현저성[실험조：（174.75±11.37）s，대조조：（194.32±14.32）s，가수술조：（169.62±19.27）s，F=6.59，P=0.005]；여대조조상비，실험조화가수술조현미불동시간현저축단；3조소서탐동차수、활동시간、활동로정차이현저（F=6.17，P=0.008；F=11.55，P＜0.001；F=13.47，P＜0.001）；여대조조상비，실험조여가수술조탐동차수명현증다[실험조：（50.86±9.23）차，대조조：（35.73±11.96）차，가수술조：（48.14±10.16）차]，활동시간여활동총로정균명현연장[실험조：（786.70±27.51）s，대조조：（738.88±36.00）s，가수술조：（807.90±33.16）s；실험조：（37171.42±8493.40）mm，대조조：（28992.91±5760.03）mm，가수술조：（47206.23±8219.84）mm]；수미궁실험잠복기차이유현저성[실험조：（87.38±13.36）s，대조조：（88.50±19.88）s，가수술조：（44.38±19.76）s，F=16.09，P＜0.001]，여가수술조상비，실험조화대조조잠복기현저연장。염증인자검측제시，3조해마TNF-α、IL-1β급IL-6차이구유현저성[실험조：（141.10±24.36）pg/100 mg，대조조：（167.6±15.91）pg/100 mg，가수술조：（123.8±15.53） pg/100 mg，F=13.42，P＜0.001；실험조：（5.32±1.89）pg/mg，대조조：（10.31±2.83）pg/mg，가수술조：（4.50±2.07）pg/mg，F=18.69，P＜0.001；실험조：（20.01±3.62）pg/mg，대조조：（24.39±5.04）pg/mg，가수술조：（18.40±3.78）pg/mg，F=5.49，P=0.010]；여대조조상비，실험조여가수술조3충염성세포인자균현저강저。3조해마5-HT급DA함량차이유현저[실험조：（3.89±1.21）ng/ml，대조조：（3.13±1.44）ng/ml，가수술조：（5.01±1.68）ng/ml，F=4.17，P=0.026；실험조：（10.72±2.65）ng/ml，대조조：（7.99±2.31）ng/ml，가수술조：（11.76±3.10）ng/ml，F=5.18，P=0.012]；여대조조상비，실험조화가수술조DA함량현저증가，실험조5-HT함량차이무현저성，이가수술조5-HT함량증다；3조NE함량차이무현저성[실험조：（3.97±1.35）ng/ml，대조조：（3.16±1.55）ng/ml，가수술조：（4.68±1.99）ng/ml，F=2.13，P=0.139]。<br> 결론 Minocycline능구억제혈관성억욱소서염증인자적표체，항염증치료가개선기억욱행위，대인지손해미관찰도명현개선，상관적신경체질이DA적개변위최명현。
Objective To investigate the effects of minocycline, a neuroinflammation inhibitor, on the depressive behaviors and neurotransmitters in the vascular depression mice model. <br> Methods Male CD1 mice were subject to repeated common carotid artery occlusion and reperfusion to establish the vascular depression model, then randomly divided into experimental group (n=10), control group (n=10) and sham group (n=10). Minocycline (30 mg/kg, i.p.) and same dose of saline were administrated immediately after the surgery and subsequently the consecutive 6 days in experimental group and control group respectively. Mice in sham group were conducted the same surgery expect occluding carotid artery, then administered the same dose of saline as the control group. After the administration, tail suspension test and open-ifeld test were used to assess depression behaviors of mice on the post operation day (POD) 8 and 9 respectively, and Morris water maze was used to assess cognitive function on the POD 10. On POD 11, mice were deeply anesthetized and euthanized and transcardially perfused with phosphate buffered saline (PBS). Expressions of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in hippocampus were measured by enzyme-linked immunosorbent assay (ELISA) kit. Contents of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA) were measured by high performance liquid chromatography (HPLC). <br> Results Among the three groups, the immobility time was signiifcantly different ([174.75±11.37]s vs [194.32±14.32]s vs [169.62±19.27]s, F=6.59, P=0.005), and the immobility time of experimental group and sham group was shorter than control group significantly. The times of exploring holes, prolonged time and distance of movement were signiifcantly different (F=6.17, P=0.008;F=11.55, P<0.001;F=13.47, P<0.001), the times of exploring holes of experimental group and sham group was more than control group signiifcantly, and so did both prolonged time and distance of movement of those two groups. But there was significant difference in escape latency ([87.38±13.36]s vs [88.50±19.88]s vs [44.38±19.76]s, F=16.09, P<0.001) among the three groups, the escape latency of experimental group and control group was signiifcantly longer than sham group. The expression of TNF-α, IL-1βand IL-6 in hippocampus were down-regulated in experimental group and sham group compared with control group (TNF-α:[141.10±24.36]pg/100 mg vs [167.6±15.91]pg/100 mg vs [123.8±15.53]pg/100 mg, F=13.42, P<0.001;IL-6:[20.01±3.62]pg/mg vs [24.39±5.04]pg/mg vs [18.40±3.78]pg/mg, F=5.49, P=0.010;IL-1β([5.32±1.89]pg/mg vs [10.31±2.83]pg/mg vs [4.50±2.07] pg/mg, F=18.69, P<0.001). There were no signiifcant difference in the level of NE among the three groups ([3.97±1.35]ng/ml vs [3.16±1.55]ng/ml vs [4.68±1.99]ng/ml, F=2.13, P=0.139), but there is a increased level of DA in experimental group and sham group compared with control group ([10.72±2.65] ng/ml, [11.76±3.10] ng/ml vs [7.99±2.31] ng/ml). <br> Conclusion Minocycline can restrain the expression of inflammatory cytokines in vascular depression mice, and inhibited inflammation may improve their depression behaviors, but no improvement found in the cognitive impairment. Among those relevant neurotransmitters, the content of DA changes most signiifcantly.
