中华生物医学工程杂志
中華生物醫學工程雜誌
중화생물의학공정잡지
CHINESE JOURNAL OF BIOMEDICAL ENGINEERING
2014年
4期
272-276
,共5页
张伟雯%孙卫文%杨泉%黄月玲%戴丽军%杨凤啸%陈盛强%孙祺章
張偉雯%孫衛文%楊泉%黃月玲%戴麗軍%楊鳳嘯%陳盛彊%孫祺章
장위문%손위문%양천%황월령%대려군%양봉소%진성강%손기장
氯化锂%小鼠,基因敲除%脆性X染色体智力低下基因1%旷场行为%脆性X综合征
氯化鋰%小鼠,基因敲除%脆性X染色體智力低下基因1%曠場行為%脆性X綜閤徵
록화리%소서,기인고제%취성X염색체지력저하기인1%광장행위%취성X종합정
Lithium chloride%Mice,knockout%Fragile X mental retardation 1 gene%Open-field behaviors%Fragile X syndrome
目的 观察氯化锂是否可以改善脆性X染色体智力低下基因1(FMR1)敲除小鼠的旷场异常行为及探讨其可能机制.方法 4周龄FMR1基因敲除小鼠(KO)和野生型小鼠(WT)各90只,按随机数字法各分为对照组(生理盐水)、氯化锂30、60、90、120、200 mg/kg组共6组,每组15只.氯化锂组小鼠连续5d腹腔注射氯化锂.观察对照组和氯化锂组KO与WT小鼠总运动长度、总跨格次数、中央区活动时间以及中央区进入次数等旷场实验行为的差异.采用免疫印迹观察氯化锂对KO与WT小鼠海马和皮层的糖原合酶激酶(GSK)3β和磷酸化(P)-GSK3β的影响.结果 对照组中KO小鼠的总运动长度、总跨格次数、中央区活动时间、中央区进入次数均比WT小鼠多(均P＜0.05).与对照组比较,氯化锂5个剂量组KO小鼠旷场实验总运动长度、总跨格次数、中央区活动时间、中央区进入次数均有明显减少(均P＜0.05);而WT小鼠用药后总运动长度和中央区活动时间在氯化锂90、120、200 mg/kg剂量组低于对照组(均P＜0.05),总跨格次数在氯化锂达到200 mg/kg剂量时才较对照组减少[(75.73±5.12)次比(125.73±9.24)次,P＜0.05],中央区进入次数则在氯化锂5个剂量组均低于对照组(均P＜0.05).对照组KO小鼠皮层和海马的GSK3β表达量与WT小鼠比较差异没有统计学意义;而P-GSK3β表达量比WT小鼠少(均P＜0.05).氯化锂组KO小鼠皮层和海马GSK3β表达与对照组比较差异没有统计学意义,而皮层P-GSK3β的表达在氯化锂120、200 mg/kg组高于对照组(均P＜0.05),海马P-GSK3β的表达在氯化锂30 ～ 200 mg/kg 5个剂量组均高于对照组(均P＜0.05).氯化锂组WT小鼠皮层和海马GSK3β和P-GSK3β的表达与对照组比较差异均没有统计学意义.使用相同剂量氯化锂的KO小鼠皮层和海马P-GSK3β表达比WT小鼠少(均P＜0.05),而GSK3β表达差异没有统计学意义.结论 氯化锂可以改善FMR1基因敲除小鼠的旷场异常行为,其机制与氯化锂导致的P-GSK3β的表达增加有关.
目的 觀察氯化鋰是否可以改善脆性X染色體智力低下基因1(FMR1)敲除小鼠的曠場異常行為及探討其可能機製.方法 4週齡FMR1基因敲除小鼠(KO)和野生型小鼠(WT)各90隻,按隨機數字法各分為對照組(生理鹽水)、氯化鋰30、60、90、120、200 mg/kg組共6組,每組15隻.氯化鋰組小鼠連續5d腹腔註射氯化鋰.觀察對照組和氯化鋰組KO與WT小鼠總運動長度、總跨格次數、中央區活動時間以及中央區進入次數等曠場實驗行為的差異.採用免疫印跡觀察氯化鋰對KO與WT小鼠海馬和皮層的糖原閤酶激酶(GSK)3β和燐痠化(P)-GSK3β的影響.結果 對照組中KO小鼠的總運動長度、總跨格次數、中央區活動時間、中央區進入次數均比WT小鼠多(均P＜0.05).與對照組比較,氯化鋰5箇劑量組KO小鼠曠場實驗總運動長度、總跨格次數、中央區活動時間、中央區進入次數均有明顯減少(均P＜0.05);而WT小鼠用藥後總運動長度和中央區活動時間在氯化鋰90、120、200 mg/kg劑量組低于對照組(均P＜0.05),總跨格次數在氯化鋰達到200 mg/kg劑量時纔較對照組減少[(75.73±5.12)次比(125.73±9.24)次,P＜0.05],中央區進入次數則在氯化鋰5箇劑量組均低于對照組(均P＜0.05).對照組KO小鼠皮層和海馬的GSK3β錶達量與WT小鼠比較差異沒有統計學意義;而P-GSK3β錶達量比WT小鼠少(均P＜0.05).氯化鋰組KO小鼠皮層和海馬GSK3β錶達與對照組比較差異沒有統計學意義,而皮層P-GSK3β的錶達在氯化鋰120、200 mg/kg組高于對照組(均P＜0.05),海馬P-GSK3β的錶達在氯化鋰30 ～ 200 mg/kg 5箇劑量組均高于對照組(均P＜0.05).氯化鋰組WT小鼠皮層和海馬GSK3β和P-GSK3β的錶達與對照組比較差異均沒有統計學意義.使用相同劑量氯化鋰的KO小鼠皮層和海馬P-GSK3β錶達比WT小鼠少(均P＜0.05),而GSK3β錶達差異沒有統計學意義.結論 氯化鋰可以改善FMR1基因敲除小鼠的曠場異常行為,其機製與氯化鋰導緻的P-GSK3β的錶達增加有關.
목적 관찰록화리시부가이개선취성X염색체지력저하기인1(FMR1)고제소서적광장이상행위급탐토기가능궤제.방법 4주령FMR1기인고제소서(KO)화야생형소서(WT)각90지,안수궤수자법각분위대조조(생리염수)、록화리30、60、90、120、200 mg/kg조공6조,매조15지.록화리조소서련속5d복강주사록화리.관찰대조조화록화리조KO여WT소서총운동장도、총과격차수、중앙구활동시간이급중앙구진입차수등광장실험행위적차이.채용면역인적관찰록화리대KO여WT소서해마화피층적당원합매격매(GSK)3β화린산화(P)-GSK3β적영향.결과 대조조중KO소서적총운동장도、총과격차수、중앙구활동시간、중앙구진입차수균비WT소서다(균P＜0.05).여대조조비교,록화리5개제량조KO소서광장실험총운동장도、총과격차수、중앙구활동시간、중앙구진입차수균유명현감소(균P＜0.05);이WT소서용약후총운동장도화중앙구활동시간재록화리90、120、200 mg/kg제량조저우대조조(균P＜0.05),총과격차수재록화리체도200 mg/kg제량시재교대조조감소[(75.73±5.12)차비(125.73±9.24)차,P＜0.05],중앙구진입차수칙재록화리5개제량조균저우대조조(균P＜0.05).대조조KO소서피층화해마적GSK3β표체량여WT소서비교차이몰유통계학의의;이P-GSK3β표체량비WT소서소(균P＜0.05).록화리조KO소서피층화해마GSK3β표체여대조조비교차이몰유통계학의의,이피층P-GSK3β적표체재록화리120、200 mg/kg조고우대조조(균P＜0.05),해마P-GSK3β적표체재록화리30 ～ 200 mg/kg 5개제량조균고우대조조(균P＜0.05).록화리조WT소서피층화해마GSK3β화P-GSK3β적표체여대조조비교차이균몰유통계학의의.사용상동제량록화리적KO소서피층화해마P-GSK3β표체비WT소서소(균P＜0.05),이GSK3β표체차이몰유통계학의의.결론 록화리가이개선FMR1기인고제소서적광장이상행위,기궤제여록화리도치적P-GSK3β적표체증가유관.
Objective To study the effects and potential mechanisms of lithium chloride on openfield behaviors of fragile X mental retardation 1 gene (FMR1) knockout mice (KO mice).Methods 4-weekold KO mice (n=90) and their wild type counterparts (WT mice,n=90) were,by using random number table,assigned to control group (intraperitoneally injected with normal saline,n=15) and 5 treatment groups intraperitoneally injected with 30 mg/kg (n=15),60 mg/kg (n=15),90 mg/kg (n=15),120 mg/kg (n=15) and 200 mg/kg lithium chloride (n=15) for 5 consecutive days,respectively.The differences in the total length of running,total number of region crossings,and the duration and number of central region crossings of all groups were determined in open field tests.Meanwhile,Western blotting was used to observe the expression of glycogen synthase kinase3β (GSK3β) and phosphorylated glycogen synthase kinase3β (PGSK3β) in the hippocampus and cortex of KO and WT mice.Results KO mice had longer distance of movements,greater total number of region crossings,longer duration and greater number of central region crossings than WT mice (all P＜0.05).Compared with control group,administration of lithium chloride resulted in significantly reduced distance of movements,total number of region crossings,shorter duration and smaller number of central region crossings (all P＜0.05) in KO mice.Lithium chloride administration (90,120 and 200 mg/kg) was associated with shorter distance of movements and duration of central region crossings in WT mice as compared with control group (all P＜0.05).200 mg/kg,but not 30 to 120 mg/kg,lithium chloride led to reduced total number of region crossings compared with control group (75.73±5.12 vs 125.73±9.24,P＜0.05).However,lithium chloride administration was associated with a reduced number of central region crossings compared with control group (all P＜0.05).No significant difference was found in hippocampus and cortex GSK3β,but not P-GSK3β,expression between KO mice and WT mice in control group (P＞0.05).There were no significant differences in hippocampus and cortex GSK3β expression between KO mice and WT mice in lithium chloride treatment groups.Compared with control group,the cortex P-GSK3β expression was significantly higher in 120 and 200 mg/kg lithium chloride groups (both P＜ 0.05),and the hippocampus GSK3β expression was up-regulated in all lithium chloride treatment groups (all P＜0.05).In lithium chloride treatment groups,the difference in hippocampus and cortex GSK3β,as well as P-GSK3β,expression failed to reach statistical significance (both P＞0.05).Using the same dose of lithium chloride administration,hippocampus and cortex P-GSK3β (but not GSK3β) expression in KO mice was lessthan that in WT mice.Conclusion Lithium chloride ameliorates aberrant open-field behaviors of KO mice,which may be related to the up-regulation of P-GSK3β expression.
