中华行为医学与脑科学杂志
中華行為醫學與腦科學雜誌
중화행위의학여뇌과학잡지
CHINESE JOURNAL OF BEHAVIORAL MEDICINE AND BRAIN SCIENCE
2015年
7期
584-587
,共4页
17β-雌二醇%氯胺酮%皮层区%Morris水迷宫%乙酰胆碱酯酶%乙酰胆碱
17β-雌二醇%氯胺酮%皮層區%Morris水迷宮%乙酰膽堿酯酶%乙酰膽堿
17β-자이순%록알동%피층구%Morris수미궁%을선담감지매%을선담감
17β-estradiol%Ketamine%Prefrontal cortex%Morris water maze%Acetylcholine esterase%Acetylcholine
目的 探讨17β-雌二醇对氯胺酮所致发育期大鼠远期学习记忆损伤的影响以及机制.方法 80只7d龄雄性SD大鼠,随机数字表法分为对照组(C组),溶剂对照组(V组),17β-雌二醇组(E组),氯胺酮组(K组),氯胺酮+17β-雌二醇组(K+E组),每组16只.C组连续3d腹腔注射等容量生理盐水,V组连续3d皮下注射等容量麻油,E组连续3d皮下注射600 μg·kg-1 17β-雌二醇,K组连续3d腹腔注射75 mg·kg-1氯胺酮,K+E组连续3d腹腔注射75 mg·kg-1氯胺酮,皮下注射600 μg·kg-1 17β-雌二醇.各组大鼠饲养至60 d时,采用Morris水迷宫观察各组大鼠行为学变化,行为学测试结束后各组取10只大鼠用ELISA法检测大脑皮层乙酰胆碱酯酶(AchE)活性,用碱性羟胺比色法测定乙酰胆碱(Ach)含量.结果 定位航行试验,K组大鼠第3,4,5天,逃避潜伏期[(40.26±2.36)s,(30.25±2.20)s,(21.55±2.42)s]与游泳距离[(1019.35±58.13) cm,(811.16±27.58) cm,(598.34±34.74) cm]均较C组显著延长(均P＜0.05),K+E组逃避潜伏期[(29.46±2.20)s,(24.86±2.14)s,(17.20±1.91)s]与游泳距离[(913.90±41.89)cm,(729.42±31.36)cm,(487.64±18.61)cm)]均较K组显著降低(均P＜0.05).第6天行空间探索实验,K组第四象限百分比[(24.5±2.7)％]及穿越平台次数[(1.9±0.5)次]均较C组显著降低(均P＜0.05),K+E组第四象限百分比[(42.3±3.0)％]及穿越平台次数[(3.5±0.5)次]均较K组显著升高(均P＜0.05).K组AchE活力[(0.69±0.04)U·mg pro-1]较C组[(0.52±0.06)U·mg pro-1]显著升高(P＜0.05),K+E组AchE活力[(0.58±0.12)U·mg pro-1]较K组显著下降(P＜0.05).K组Ach含量[(2.59±0.34)mg·g-1]较C组显著下降(P＜0.05),K+E组Ach含量[(3.88±0.61)mg·g-1]较K组显著升高(P＜0.05).结论 连续大剂量应用氯胺酮可引起发育期大鼠远期学习记忆能力损伤,17β-雌二醇可改善氯胺酮引起的远期学习记忆损伤,其机制可能与降低大脑皮层区AchE活性,提高Ach含量有关.
目的 探討17β-雌二醇對氯胺酮所緻髮育期大鼠遠期學習記憶損傷的影響以及機製.方法 80隻7d齡雄性SD大鼠,隨機數字錶法分為對照組(C組),溶劑對照組(V組),17β-雌二醇組(E組),氯胺酮組(K組),氯胺酮+17β-雌二醇組(K+E組),每組16隻.C組連續3d腹腔註射等容量生理鹽水,V組連續3d皮下註射等容量痳油,E組連續3d皮下註射600 μg·kg-1 17β-雌二醇,K組連續3d腹腔註射75 mg·kg-1氯胺酮,K+E組連續3d腹腔註射75 mg·kg-1氯胺酮,皮下註射600 μg·kg-1 17β-雌二醇.各組大鼠飼養至60 d時,採用Morris水迷宮觀察各組大鼠行為學變化,行為學測試結束後各組取10隻大鼠用ELISA法檢測大腦皮層乙酰膽堿酯酶(AchE)活性,用堿性羥胺比色法測定乙酰膽堿(Ach)含量.結果 定位航行試驗,K組大鼠第3,4,5天,逃避潛伏期[(40.26±2.36)s,(30.25±2.20)s,(21.55±2.42)s]與遊泳距離[(1019.35±58.13) cm,(811.16±27.58) cm,(598.34±34.74) cm]均較C組顯著延長(均P＜0.05),K+E組逃避潛伏期[(29.46±2.20)s,(24.86±2.14)s,(17.20±1.91)s]與遊泳距離[(913.90±41.89)cm,(729.42±31.36)cm,(487.64±18.61)cm)]均較K組顯著降低(均P＜0.05).第6天行空間探索實驗,K組第四象限百分比[(24.5±2.7)％]及穿越平檯次數[(1.9±0.5)次]均較C組顯著降低(均P＜0.05),K+E組第四象限百分比[(42.3±3.0)％]及穿越平檯次數[(3.5±0.5)次]均較K組顯著升高(均P＜0.05).K組AchE活力[(0.69±0.04)U·mg pro-1]較C組[(0.52±0.06)U·mg pro-1]顯著升高(P＜0.05),K+E組AchE活力[(0.58±0.12)U·mg pro-1]較K組顯著下降(P＜0.05).K組Ach含量[(2.59±0.34)mg·g-1]較C組顯著下降(P＜0.05),K+E組Ach含量[(3.88±0.61)mg·g-1]較K組顯著升高(P＜0.05).結論 連續大劑量應用氯胺酮可引起髮育期大鼠遠期學習記憶能力損傷,17β-雌二醇可改善氯胺酮引起的遠期學習記憶損傷,其機製可能與降低大腦皮層區AchE活性,提高Ach含量有關.
목적 탐토17β-자이순대록알동소치발육기대서원기학습기억손상적영향이급궤제.방법 80지7d령웅성SD대서,수궤수자표법분위대조조(C조),용제대조조(V조),17β-자이순조(E조),록알동조(K조),록알동+17β-자이순조(K+E조),매조16지.C조련속3d복강주사등용량생리염수,V조련속3d피하주사등용량마유,E조련속3d피하주사600 μg·kg-1 17β-자이순,K조련속3d복강주사75 mg·kg-1록알동,K+E조련속3d복강주사75 mg·kg-1록알동,피하주사600 μg·kg-1 17β-자이순.각조대서사양지60 d시,채용Morris수미궁관찰각조대서행위학변화,행위학측시결속후각조취10지대서용ELISA법검측대뇌피층을선담감지매(AchE)활성,용감성간알비색법측정을선담감(Ach)함량.결과 정위항행시험,K조대서제3,4,5천,도피잠복기[(40.26±2.36)s,(30.25±2.20)s,(21.55±2.42)s]여유영거리[(1019.35±58.13) cm,(811.16±27.58) cm,(598.34±34.74) cm]균교C조현저연장(균P＜0.05),K+E조도피잠복기[(29.46±2.20)s,(24.86±2.14)s,(17.20±1.91)s]여유영거리[(913.90±41.89)cm,(729.42±31.36)cm,(487.64±18.61)cm)]균교K조현저강저(균P＜0.05).제6천행공간탐색실험,K조제사상한백분비[(24.5±2.7)％]급천월평태차수[(1.9±0.5)차]균교C조현저강저(균P＜0.05),K+E조제사상한백분비[(42.3±3.0)％]급천월평태차수[(3.5±0.5)차]균교K조현저승고(균P＜0.05).K조AchE활력[(0.69±0.04)U·mg pro-1]교C조[(0.52±0.06)U·mg pro-1]현저승고(P＜0.05),K+E조AchE활력[(0.58±0.12)U·mg pro-1]교K조현저하강(P＜0.05).K조Ach함량[(2.59±0.34)mg·g-1]교C조현저하강(P＜0.05),K+E조Ach함량[(3.88±0.61)mg·g-1]교K조현저승고(P＜0.05).결론 련속대제량응용록알동가인기발육기대서원기학습기억능력손상,17β-자이순가개선록알동인기적원기학습기억손상,기궤제가능여강저대뇌피층구AchE활성,제고Ach함량유관.
Objective To investigate the effect of 17β-estradiol on ketamine-induced long-term cognitive deficits in neonatal rats.Methods 80 SD male rats aged 7 days were randomly divided into group C,V,E,K and K+E,and 16 per group.Group C was intraperitoneally injected with same volume of saline for three consecutive days,Group V was subcutaneously injected with same volume of sesame oil for three consecutive days,Group E was subcutaneously injected with 600 μg · kg-1 17β-estradiol for three consecutive days,group K was intraperitoneally injected with 75 mg · kg-1 ketamine for three consecutive days,group K+E was intraperitoneally injected with 75 mg · kg-1 ketamine in combination with 600 μg · kg-1 17β-estradiol injected subcutaneously for three consecutive days.At 2 months of age,learning and memory abilities were tested with the Mortis water maze.After Morris water naze test,ten rats from each group were decapitated and the prefrontal cortex (PFC) was isolated to detect acetylcholine esterase(AchE) activity with ELISA assay and to measure acetylcholine(Ach) level by hydroxylammonium chloride method.Results The escape latency ((40.26±2.36) s,(30.25±2.20) s,(21.55±2.42) s) and path length((1019.35±58.13) cm,(811.16±27.58) cm,(598.34±34.74) cm) of group K were more than those of group C on the third,fourth aud fifth training days (all P＜0.05),while escape latency ((29.46±2.20) s,(24.86± 2.14) s,(17.20±1.91) s) and path length((913.90±41.89) cm,(729.42±31.36) cm,(487.64±18.61)cm) of group K+E were significantly lower than those of group K(all P＜0.05).On test day 6,rats were subjected to a probe trial,ratio of time spent in the target quadrant ((24.5±2.7) ％) and the number of crossings over previous platform locations (1.9±0.5) in group K were fewer than those of group C (all P＜0.05),while ratio of time spent iu the target quadrant((42.3±3.0) ％) and the number of crossings over previous platform locations(3.5±0.5) of group K+E were more than those of group K (all P＜0.05).The AchE activity((0.69±0.04) U · mg pro-1) in rats PFC of group K was significantly higher than that of group C ((0.52±0.06) U · mg pro-1) (P＜0.05).The AchE activity of group K +E ((0.58±0.12)U · mg pro-1) was lower than that of group K(P＜0.05).The Ach level ((2.59±0.34)mg · g-1) in rats PFC of group K was significantly lower than that of group C ((4.35±0.56) mg · g-1) (P＜0.05).The Ach level of group K+E((3.88±0.61) mg · g-1) was higher than that of group K(P＜0.05).Conclusions These results indicate that ketamine impairs learning and memory abilities as rat matures,while 17β-estradiol treatment improves these impairments by inhibiting AchE activity and increasing Ach level.
