中华精神科杂志
中華精神科雜誌
중화정신과잡지
CHINESE JOURNA OF PSYCHIATRY
2015年
3期
182-187
,共6页
刘蒙%李新娟%李爽%张利彬%韩金红%赵营%张瑞岭
劉矇%李新娟%李爽%張利彬%韓金紅%趙營%張瑞嶺
류몽%리신연%리상%장리빈%한금홍%조영%장서령
喹硫平%酒精%髓鞘损伤%髓鞘碱性蛋白
喹硫平%酒精%髓鞘損傷%髓鞘堿性蛋白
규류평%주정%수초손상%수초감성단백
Quetiapine%Alcohol%Myelin damage%Myelin basic protein
目的 探讨喹硫平对慢性酒精暴露C57BL/6小鼠行为以及胼胝体髓鞘形态、髓鞘碱性蛋白(myelin basic protein,MBP)表达的影响.方法 120只雄性C57BL/6小鼠,采用随机数字表法分为6组(对照组、喹硫平组、酒精模型组、喹硫平低剂量干预组、喹硫平中剂量干预组、喹硫平高剂量干预组),每组20只.酒精模型组及喹硫平干预组自由饮用体积分数为10％的酒精水溶液20周,喹硫平干预组在饮用酒精水溶液6周后分别加入5、10、15 mg·kg-1·d-1的喹硫平干预至20周,喹硫平组饮用纯净水6周后改为10 mg·kg-1·d-1的喹硫平水溶液至20周,对照组饮用纯净水20周.造模结束后,采用Morris水迷宫测试各组小鼠学习记忆变化;采用劳克坚牢蓝(luxol fast blue,LFB)染色和电子显微镜观察胼胝体髓鞘形态以及超微结构的改变;免疫荧光法检测小鼠胼胝体MBP表达变化.结果 (1)各组小鼠学习记忆测试结果组间差异有统计学意义(F=4.702,P=0.002),酒精模型组潜伏期[(22.8±5.5)s]大于对照组[(11.5±7.1) s;t=3.546,P＜0.05];喹硫平低、中剂量干预组[(19.1±8.8)s、(20.1±8.3)s]与酒精模型组比较差异均无统计学意义(t=0.989、0.748,均P＞0.05);喹硫平高剂量干预组潜伏期[(11.5±5.8)s]小于酒精模型组(t=3.998,P＜0.05);喹硫平组潜伏期[(10.6±5.5)s]与对照组相比差异无统计学意义(t=0.276,P＞0.05).(2)LFB染色及电镜结果显示酒精模型组、喹硫平低剂量干预组与对照组相比胼胝体髓鞘有明显的损伤;喹硫平中、高剂量干预组与酒精模型组相比髓鞘完整性有明显的改善;喹硫平组与对照组相比差异无统计学意义.(3)免疫荧光结果显示各组小鼠胼胝体MBP表达组间差异有统计学意义(F=28.971,P＜0.01),酒精模型组MBP表达(0.038±0.005)明显低于对照组(0.062±0.005;t=8.628,P＜0.05);喹硫平低剂量干预组(0.043±0.003)与酒精模型组相比差异无统计学意义(t=2.081,P＞0.05),喹硫平中、高剂量干预组(0.047±0.04、0.058±0.006)均高于酒精模型组(t=3.301、6.645,均P＜0.05);喹硫平组(0.061±0.005)、喹硫平高剂量干预组与对照组相比差异均无统计学意义(t=0.041、1.137,均P＞0.05).结论 慢性酒精暴露造成小鼠胼胝体白质髓鞘损伤,学习记忆能力下降;喹硫平中、高剂量干预可能会减轻或者防止慢性酒精使用引起的脑白质髓鞘损伤.
目的 探討喹硫平對慢性酒精暴露C57BL/6小鼠行為以及胼胝體髓鞘形態、髓鞘堿性蛋白(myelin basic protein,MBP)錶達的影響.方法 120隻雄性C57BL/6小鼠,採用隨機數字錶法分為6組(對照組、喹硫平組、酒精模型組、喹硫平低劑量榦預組、喹硫平中劑量榦預組、喹硫平高劑量榦預組),每組20隻.酒精模型組及喹硫平榦預組自由飲用體積分數為10％的酒精水溶液20週,喹硫平榦預組在飲用酒精水溶液6週後分彆加入5、10、15 mg·kg-1·d-1的喹硫平榦預至20週,喹硫平組飲用純淨水6週後改為10 mg·kg-1·d-1的喹硫平水溶液至20週,對照組飲用純淨水20週.造模結束後,採用Morris水迷宮測試各組小鼠學習記憶變化;採用勞剋堅牢藍(luxol fast blue,LFB)染色和電子顯微鏡觀察胼胝體髓鞘形態以及超微結構的改變;免疫熒光法檢測小鼠胼胝體MBP錶達變化.結果 (1)各組小鼠學習記憶測試結果組間差異有統計學意義(F=4.702,P=0.002),酒精模型組潛伏期[(22.8±5.5)s]大于對照組[(11.5±7.1) s;t=3.546,P＜0.05];喹硫平低、中劑量榦預組[(19.1±8.8)s、(20.1±8.3)s]與酒精模型組比較差異均無統計學意義(t=0.989、0.748,均P＞0.05);喹硫平高劑量榦預組潛伏期[(11.5±5.8)s]小于酒精模型組(t=3.998,P＜0.05);喹硫平組潛伏期[(10.6±5.5)s]與對照組相比差異無統計學意義(t=0.276,P＞0.05).(2)LFB染色及電鏡結果顯示酒精模型組、喹硫平低劑量榦預組與對照組相比胼胝體髓鞘有明顯的損傷;喹硫平中、高劑量榦預組與酒精模型組相比髓鞘完整性有明顯的改善;喹硫平組與對照組相比差異無統計學意義.(3)免疫熒光結果顯示各組小鼠胼胝體MBP錶達組間差異有統計學意義(F=28.971,P＜0.01),酒精模型組MBP錶達(0.038±0.005)明顯低于對照組(0.062±0.005;t=8.628,P＜0.05);喹硫平低劑量榦預組(0.043±0.003)與酒精模型組相比差異無統計學意義(t=2.081,P＞0.05),喹硫平中、高劑量榦預組(0.047±0.04、0.058±0.006)均高于酒精模型組(t=3.301、6.645,均P＜0.05);喹硫平組(0.061±0.005)、喹硫平高劑量榦預組與對照組相比差異均無統計學意義(t=0.041、1.137,均P＞0.05).結論 慢性酒精暴露造成小鼠胼胝體白質髓鞘損傷,學習記憶能力下降;喹硫平中、高劑量榦預可能會減輕或者防止慢性酒精使用引起的腦白質髓鞘損傷.
목적 탐토규류평대만성주정폭로C57BL/6소서행위이급변지체수초형태、수초감성단백(myelin basic protein,MBP)표체적영향.방법 120지웅성C57BL/6소서,채용수궤수자표법분위6조(대조조、규류평조、주정모형조、규류평저제량간예조、규류평중제량간예조、규류평고제량간예조),매조20지.주정모형조급규류평간예조자유음용체적분수위10％적주정수용액20주,규류평간예조재음용주정수용액6주후분별가입5、10、15 mg·kg-1·d-1적규류평간예지20주,규류평조음용순정수6주후개위10 mg·kg-1·d-1적규류평수용액지20주,대조조음용순정수20주.조모결속후,채용Morris수미궁측시각조소서학습기억변화;채용로극견뢰람(luxol fast blue,LFB)염색화전자현미경관찰변지체수초형태이급초미결구적개변;면역형광법검측소서변지체MBP표체변화.결과 (1)각조소서학습기억측시결과조간차이유통계학의의(F=4.702,P=0.002),주정모형조잠복기[(22.8±5.5)s]대우대조조[(11.5±7.1) s;t=3.546,P＜0.05];규류평저、중제량간예조[(19.1±8.8)s、(20.1±8.3)s]여주정모형조비교차이균무통계학의의(t=0.989、0.748,균P＞0.05);규류평고제량간예조잠복기[(11.5±5.8)s]소우주정모형조(t=3.998,P＜0.05);규류평조잠복기[(10.6±5.5)s]여대조조상비차이무통계학의의(t=0.276,P＞0.05).(2)LFB염색급전경결과현시주정모형조、규류평저제량간예조여대조조상비변지체수초유명현적손상;규류평중、고제량간예조여주정모형조상비수초완정성유명현적개선;규류평조여대조조상비차이무통계학의의.(3)면역형광결과현시각조소서변지체MBP표체조간차이유통계학의의(F=28.971,P＜0.01),주정모형조MBP표체(0.038±0.005)명현저우대조조(0.062±0.005;t=8.628,P＜0.05);규류평저제량간예조(0.043±0.003)여주정모형조상비차이무통계학의의(t=2.081,P＞0.05),규류평중、고제량간예조(0.047±0.04、0.058±0.006)균고우주정모형조(t=3.301、6.645,균P＜0.05);규류평조(0.061±0.005)、규류평고제량간예조여대조조상비차이균무통계학의의(t=0.041、1.137,균P＞0.05).결론 만성주정폭로조성소서변지체백질수초손상,학습기억능력하강;규류평중、고제량간예가능회감경혹자방지만성주정사용인기적뇌백질수초손상.
Objective To observe the effects of quetiapine on cognitive function,myelin morphology and expression of myelin basic protein in the corpus callosum of C57BL/6 mice with chronic alcohol exposure.Methods According to random number table,120 male C57BL/6 mice were divided into 6 groups,i.e.,control group,quetiapine control group (10 mg· kg-1· d-1quetiapine),alcohol group,5 mg· kg-1· d1quetiapine plus alcohol group,10 mg· kg-1· d-1 quetiapine plus alcohol group and 15 mg·kg-1· d-1quetiapine plus alcohol group,with 20 mice in each group.Mice in control group and quetiapine control group were maintained with water and solid diet for 20 weeks.Mice in alcohol group and quetiapine plus alcohol groups were maintained with water containing volume fraction of 10％ alcohol and solid diet for 20 weeks.Drug with different doses was dissolved in mice drinking for intervention beginning at the 6th week and continuing to the end of the experiment.Morris water maze experiment was used to test the cognitive function.Luxol fast blue (LFB) staining and electron microscopy were used to observe morphology of corpus callosum.The expression of myelin basic protein in the corpus callosum was evaluated with immunofluorescence.Results (1)Morris water maze test showed that the cognition of mice in each group was different (F=4.702,P=0.002).The latency of mice in alcohol group ((22.8 ±5.5) s) was significantly longer compared with that of the control group((1 1.5± 7.1) s,t=3.546,P＜0.05).The latency of 5 mg· kg1 · d-1and 10 mg· kg-1 · d-1quetiapine plus alcohol groups ((19.1±8.8) s,(20.1±8.3) s) were not significantly different compared with that of the alcohol group (t=0.989,0.748,both P＞0.05).The latency of 15 mg· kg-1· d-1quetiapine plus alcohol group((11.5 ± 5.8) s) was significantly shorter compared with that of the alcohol group (t=3.998,P＜0.05).The latency of quetiapine control group ((10.6±5.5) s) was not significantly different compared with that of the control group (t=0.276,P＞0.05).(2)LFB staining and electron microscope results showed severe myelin damage in the corpus callosum of mice in alcohol group,while the integrity of the myelin sheath in 10 mg· kg-1· d 1and 15 mg·kg-1· d-1quetiapine plus alcohol groups improved significantly compared with the alcohol group.The integrity of the myelin sheath in quetiapine control group was not significantly different compared with that of the control group.(3) Inmunofluorescence results showed that the expression of myelin basic protein of each group was different (F=28.971,P＜0.01).The expression of myelin basic protein in alcohol group (0.038±0.005) was significantly decreased compared to the control group (0.062±0.005,t=8.628,P＜0.05).The expression of myelin basic protein in 5 mg·kg-1· d-1 quetiapine plus alcohol group (0.043±0.003)was not significantly different compared with the alcohol group (t=2.081,P＞0.05).The expression of myelin basic protein of 10 mg·kg-1· d-1 and 15 mg·kg-1· d-1 quetiapine plus alcohol groups (0.047±0.04,0.058±0.006) were significantly increased compared with the alcohol group (t=3.301,6.645,both P＜0.05).The expression of myelin basic protein in quetiapine control group (0.061±0.005)was not significantly different compared with the control group (t=0.041,1.137,both P＞0.05).Conclusion Chronic alcohol exposure could induce cognition impairment and white matter myelin danage in mice.Quetiapine treatment may prevent the brain white matter damage due to chronic alcohol exposure in mice.
