中华神经科杂志
中華神經科雜誌
중화신경과잡지
Chinese Journal of Neurology
2010年
9期
626-631
,共6页
王东%张临洪%徐威%杜小霞%湛言强%张苏明
王東%張臨洪%徐威%杜小霞%湛言彊%張囌明
왕동%장림홍%서위%두소하%담언강%장소명
阿尔茨海默病%小鼠,转基因%铁%衰老斑%磁共振成像%时间
阿爾茨海默病%小鼠,轉基因%鐵%衰老斑%磁共振成像%時間
아이자해묵병%소서,전기인%철%쇠로반%자공진성상%시간
Alzheimer disease%Mice,transgenic%Iron%Senile plaques%Magnetic resonance imaging%Time
目的 观察老年斑和铁在阿尔茨海默病(AD)转基因小鼠脑内皮质和海马处的沉积及其对磁共振活体扫描T2弛豫时间的影响.方法 2、4、6、8、10、12、14、16月龄的AD转基因小鼠各2只,分为幼龄组、成龄组和老龄组,8月龄野生型C57BL/6J小鼠2只作为对照,依次进行磁共振活体扫描,测量皮质、海马、丘脑、胼胝体、纹状体等结构的T2弛豫时间,扫描完成后,进行铁和老年斑的组织学染色,计算皮质和海马处老年斑的数目及含量、铁颗粒的数目及含量.结果 各组皮质及海马T2弛豫时间(ms)分别为:野生组:49.5±2.1、51.6±1.1;幼龄组(2、4月龄):49.7±0.5、50.7±0.7;成龄组(6、8、10月龄):47.2±0.8、47.7±0.9;老龄组(12、14、16月龄):44.6±0.8、45.3±0.4.各组皮质及海马T2弛豫时间差异有统计学意义(皮质F=18.620,海马F=67.925,均P＜0.01).组间比较示成龄组较幼龄组(皮质q=4.284,海马q=7.902;均P＜0.01)及野生组(皮质q=4.424,P＜0.05,海马q=11.450,P＜0.01)小鼠皮质及海马T2弛豫时间缩短;而老龄组较成龄组小鼠皮质及海马T2弛豫时间缩短(皮质q=4.812,海马q=7.034,均P＜0.01).组织学染色示4月龄转基因小鼠皮质和海马开始出现老年斑的沉积,6月龄开始出现铁的沉积,并且随着小鼠月龄的增加,皮质和海马处老年斑和铁的数目及含量均明显增加.老年斑和铁的沉积具有明显的正相关(r=0.931,P＜0.01),老年斑的含量、铁的含量与T2弛豫时间均具有明显的负相关(分别r=-0.884、-0.827,均P＜0.01).结论 老年斑和铁的沉积可能共同影响T2弛豫时间,提示T2弛豫时间可以作为早期诊断AD和抗痴呆药物筛选的一个敏感性指标.
目的 觀察老年斑和鐵在阿爾茨海默病(AD)轉基因小鼠腦內皮質和海馬處的沉積及其對磁共振活體掃描T2弛豫時間的影響.方法 2、4、6、8、10、12、14、16月齡的AD轉基因小鼠各2隻,分為幼齡組、成齡組和老齡組,8月齡野生型C57BL/6J小鼠2隻作為對照,依次進行磁共振活體掃描,測量皮質、海馬、丘腦、胼胝體、紋狀體等結構的T2弛豫時間,掃描完成後,進行鐵和老年斑的組織學染色,計算皮質和海馬處老年斑的數目及含量、鐵顆粒的數目及含量.結果 各組皮質及海馬T2弛豫時間(ms)分彆為:野生組:49.5±2.1、51.6±1.1;幼齡組(2、4月齡):49.7±0.5、50.7±0.7;成齡組(6、8、10月齡):47.2±0.8、47.7±0.9;老齡組(12、14、16月齡):44.6±0.8、45.3±0.4.各組皮質及海馬T2弛豫時間差異有統計學意義(皮質F=18.620,海馬F=67.925,均P＜0.01).組間比較示成齡組較幼齡組(皮質q=4.284,海馬q=7.902;均P＜0.01)及野生組(皮質q=4.424,P＜0.05,海馬q=11.450,P＜0.01)小鼠皮質及海馬T2弛豫時間縮短;而老齡組較成齡組小鼠皮質及海馬T2弛豫時間縮短(皮質q=4.812,海馬q=7.034,均P＜0.01).組織學染色示4月齡轉基因小鼠皮質和海馬開始齣現老年斑的沉積,6月齡開始齣現鐵的沉積,併且隨著小鼠月齡的增加,皮質和海馬處老年斑和鐵的數目及含量均明顯增加.老年斑和鐵的沉積具有明顯的正相關(r=0.931,P＜0.01),老年斑的含量、鐵的含量與T2弛豫時間均具有明顯的負相關(分彆r=-0.884、-0.827,均P＜0.01).結論 老年斑和鐵的沉積可能共同影響T2弛豫時間,提示T2弛豫時間可以作為早期診斷AD和抗癡呆藥物篩選的一箇敏感性指標.
목적 관찰노년반화철재아이자해묵병(AD)전기인소서뇌내피질화해마처적침적급기대자공진활체소묘T2이예시간적영향.방법 2、4、6、8、10、12、14、16월령적AD전기인소서각2지,분위유령조、성령조화노령조,8월령야생형C57BL/6J소서2지작위대조,의차진행자공진활체소묘,측량피질、해마、구뇌、변지체、문상체등결구적T2이예시간,소묘완성후,진행철화노년반적조직학염색,계산피질화해마처노년반적수목급함량、철과립적수목급함량.결과 각조피질급해마T2이예시간(ms)분별위:야생조:49.5±2.1、51.6±1.1;유령조(2、4월령):49.7±0.5、50.7±0.7;성령조(6、8、10월령):47.2±0.8、47.7±0.9;노령조(12、14、16월령):44.6±0.8、45.3±0.4.각조피질급해마T2이예시간차이유통계학의의(피질F=18.620,해마F=67.925,균P＜0.01).조간비교시성령조교유령조(피질q=4.284,해마q=7.902;균P＜0.01)급야생조(피질q=4.424,P＜0.05,해마q=11.450,P＜0.01)소서피질급해마T2이예시간축단;이노령조교성령조소서피질급해마T2이예시간축단(피질q=4.812,해마q=7.034,균P＜0.01).조직학염색시4월령전기인소서피질화해마개시출현노년반적침적,6월령개시출현철적침적,병차수착소서월령적증가,피질화해마처노년반화철적수목급함량균명현증가.노년반화철적침적구유명현적정상관(r=0.931,P＜0.01),노년반적함량、철적함량여T2이예시간균구유명현적부상관(분별r=-0.884、-0.827,균P＜0.01).결론 노년반화철적침적가능공동영향T2이예시간,제시T2이예시간가이작위조기진단AD화항치태약물사선적일개민감성지표.
Objective To observe senile plaque and iron deposition in cortex and hippocampus of the Alzheimer's disease ( AD ) transgenic mice and investigate their influence on T2 relaxation time.Method All AD transgeic mice were divided into three groups: young group(2,4 months), adult group (6,8,10 months), old group (12,14,16 months), and C57BL/6J mice were as control and were scanned in order by using 4.7 T MR system.Regions of interest (ROI) corresponding to cortex, hippocampus,thalamus, striatum were manually drawn on MR images and T2 MR relaxation times of each ROI were calculated.After MR scan, these mice were decapitated and stained for iron and senile palques.The number of plaque and iron, plaque burden, iron load in cortex and hippocampus were acquired using image pro plus software.Result T2 relaxation times of each group were as following: wild type ( cortex (49.5 ± 2.1 ) ms,hippocampus (51.6 ± 1.1 ) ms ); young ( cortex ( 49.7 ± 0.5 ) ms, hippocampus ( 50.7 ± 0.7 ) ms ); adult (cortex(47.2 ±0.8) ms, hippocampus(47.7 ±0.9) ms) and old (cortex(44.6 ±0.8) ms, hippocampus (45.3 ±0.4)ms).T2 relaxation times in cortex and hippocampus of each group had statistical differences ( cortex F = 18.620, P ＜ 0.01; hippocampus F = 67.925, P ＜ 0.01 ); Compared with young group and wild type mice, T2 relaxation times in corex and hippocampus of adult group mice were decreased significantly.At the same time, T2 relaxation times in old group mice were reduced compared with adult group ( Adult vs young: cortex q =4.284, P ＜0.01, hippocampus q =7.902, P ＜0.01; adult vs wild type: cortex q =4.424, P＜0.05, hippocampus q = 11.450, P ＜0.01; old w adult: cortex q =4.812, P ＜0.01,hippocampus q = 7.034, P ＜ 0.01 ).Histochemical staining for senile plaques found that senile plaques was deposited as early as 4 month.Iron deposition in hippocampus and cortex were detected by perl-DAB as early as 6 months of age, and there was an overall increase in number and load of plaques and iron with age.A positive correlation was observed between plaque burden and iron load ( r = 0.931, P ＜ 0.01 ).At the same time, plaque burden and iron load were negatively correlated with T2 relaxation times ( plaque burden and T2 relaxation times r = - 0.884, P ＜ 0.01; iron load and T2 relaxation times r = - 0.827, P ＜ 0.01 ).Conclusion The changes of T2 relaxation time in AD transgenic mice are attributed to iron and senile plaques.MR T2 relaxation time is a sensitive marker to diagnosis for AD and screen antidementia drugs.
