目的 观察雌激素补充时机对绝经模型大鼠空间学习和记忆力的影响,为绝经后雌激素补充时机的选择提供动物实验依据.方法 将40只SD大鼠行双侧卵巢切除术,建立绝经模型.术后将模型大鼠计算机随机分为早期激素补充治疗(HRT)组(n=10,术后3d予戊酸雌二醇补充治疗30 d)、早期对照组(n=10,术后3d予生理盐水30 d)、晚期HRT组(n=10,术后90 d予戊酸雌二醇补充治疗30 d)、晚期对照组(n=10,术后90 d予生理盐水30 d).对40只大鼠行Morris水迷宫实验测定行为学指标;并行MRI质子波谱成像技术扫描检测海马神经元代谢产物相关数据,包括N-乙酰基天冬氨酸(NAA)、胆碱化合物(Cho)、肌酸复合物(Cr)、肌醇(mI),并以Cr值为标准,计算NAA/Cr、Cho/Cr、mI/Cr、NAA/mI比值.结果 (1)Morris水迷宫定位航行实验中,逃避潜伏期:早期对照组为(43±13)s,早期HRT组为(28 ±9)s,晚期对照组为(82±26)s,晚期HRT组为(48±18)s;游泳行程:早期对照组(1 404 ±238)cm,早期HRT组(878±354)cm,晚期对照组(2 411±818)cm,晚期HRT组(1 310±434)cm;绝经模型大鼠早、晚期HRT组的逃避潜伏期及游泳行程明显较早、晚期对照组短(P<0.01).(2) Morris水迷宫空间探索实验:早期HRT组在目标象限游泳停留时间为(34.0±3.0)s,较其他各组时间长(P<0.05).(3) MRI质子波谱成像技术检测结果:NAA/Cr:早期对照组为1.12±0.17,早期HRT组1.26±0.12,晚期对照组1.57±0.21,晚期HRT组1.38±0.28,晚期HRT组和晚期对照组的NAA/Cr高于早期HRT组和早期对照组(F=6.05,P=0.040);早期HRT组与早期对照组、晚期HRT组与晚期对照组比较,差异无统计学意义(F=0.04,P=0.860).mI/Cr:早期对照组0.69±0.04,早期HRT组0.46±0.12,晚期对照组0.70±0.03,晚期HRT组0.75±0.08,晚期HRT组、晚期对照组与早期HRT组、早期对照组比较,差异有统计学意义(F=16.45,P=0.004),其中早期HRT组与早期对照组、晚期HRT组与晚期对照组组间差异明显(F =6.01,P=0.040),且实验干预的起始时间与是否HRT干预对mI/Cr存在交互作用(F=13.79,P=0.006),即早期HRT可使mI/Cr比值降低.Cho/Cr:早期对照组0.95±0.09,早期HRT组0.80±0.12,晚期对照组0.87±0.09,晚期HRT组0.85±0.12,各组绝经模型大鼠与神经细胞膜稳态有关的Cho均无明显变化,各组间比较,差异无统计学意义(P>0.05).NAA/mI:实验干预的起始时间与是否HRT干预对NAA/mI存在交互作用(F=12.95,P=0.007),早期HRT可使NAA/mI比值升高,而晚期结果则相反.结论 HRT早期干预对改善绝经模型大鼠的空间学习和记忆力有积极作用.
目的 觀察雌激素補充時機對絕經模型大鼠空間學習和記憶力的影響,為絕經後雌激素補充時機的選擇提供動物實驗依據.方法 將40隻SD大鼠行雙側卵巢切除術,建立絕經模型.術後將模型大鼠計算機隨機分為早期激素補充治療(HRT)組(n=10,術後3d予戊痠雌二醇補充治療30 d)、早期對照組(n=10,術後3d予生理鹽水30 d)、晚期HRT組(n=10,術後90 d予戊痠雌二醇補充治療30 d)、晚期對照組(n=10,術後90 d予生理鹽水30 d).對40隻大鼠行Morris水迷宮實驗測定行為學指標;併行MRI質子波譜成像技術掃描檢測海馬神經元代謝產物相關數據,包括N-乙酰基天鼕氨痠(NAA)、膽堿化閤物(Cho)、肌痠複閤物(Cr)、肌醇(mI),併以Cr值為標準,計算NAA/Cr、Cho/Cr、mI/Cr、NAA/mI比值.結果 (1)Morris水迷宮定位航行實驗中,逃避潛伏期:早期對照組為(43±13)s,早期HRT組為(28 ±9)s,晚期對照組為(82±26)s,晚期HRT組為(48±18)s;遊泳行程:早期對照組(1 404 ±238)cm,早期HRT組(878±354)cm,晚期對照組(2 411±818)cm,晚期HRT組(1 310±434)cm;絕經模型大鼠早、晚期HRT組的逃避潛伏期及遊泳行程明顯較早、晚期對照組短(P<0.01).(2) Morris水迷宮空間探索實驗:早期HRT組在目標象限遊泳停留時間為(34.0±3.0)s,較其他各組時間長(P<0.05).(3) MRI質子波譜成像技術檢測結果:NAA/Cr:早期對照組為1.12±0.17,早期HRT組1.26±0.12,晚期對照組1.57±0.21,晚期HRT組1.38±0.28,晚期HRT組和晚期對照組的NAA/Cr高于早期HRT組和早期對照組(F=6.05,P=0.040);早期HRT組與早期對照組、晚期HRT組與晚期對照組比較,差異無統計學意義(F=0.04,P=0.860).mI/Cr:早期對照組0.69±0.04,早期HRT組0.46±0.12,晚期對照組0.70±0.03,晚期HRT組0.75±0.08,晚期HRT組、晚期對照組與早期HRT組、早期對照組比較,差異有統計學意義(F=16.45,P=0.004),其中早期HRT組與早期對照組、晚期HRT組與晚期對照組組間差異明顯(F =6.01,P=0.040),且實驗榦預的起始時間與是否HRT榦預對mI/Cr存在交互作用(F=13.79,P=0.006),即早期HRT可使mI/Cr比值降低.Cho/Cr:早期對照組0.95±0.09,早期HRT組0.80±0.12,晚期對照組0.87±0.09,晚期HRT組0.85±0.12,各組絕經模型大鼠與神經細胞膜穩態有關的Cho均無明顯變化,各組間比較,差異無統計學意義(P>0.05).NAA/mI:實驗榦預的起始時間與是否HRT榦預對NAA/mI存在交互作用(F=12.95,P=0.007),早期HRT可使NAA/mI比值升高,而晚期結果則相反.結論 HRT早期榦預對改善絕經模型大鼠的空間學習和記憶力有積極作用.
목적 관찰자격소보충시궤대절경모형대서공간학습화기억력적영향,위절경후자격소보충시궤적선택제공동물실험의거.방법 장40지SD대서행쌍측란소절제술,건립절경모형.술후장모형대서계산궤수궤분위조기격소보충치료(HRT)조(n=10,술후3d여무산자이순보충치료30 d)、조기대조조(n=10,술후3d여생리염수30 d)、만기HRT조(n=10,술후90 d여무산자이순보충치료30 d)、만기대조조(n=10,술후90 d여생리염수30 d).대40지대서행Morris수미궁실험측정행위학지표;병행MRI질자파보성상기술소묘검측해마신경원대사산물상관수거,포괄N-을선기천동안산(NAA)、담감화합물(Cho)、기산복합물(Cr)、기순(mI),병이Cr치위표준,계산NAA/Cr、Cho/Cr、mI/Cr、NAA/mI비치.결과 (1)Morris수미궁정위항행실험중,도피잠복기:조기대조조위(43±13)s,조기HRT조위(28 ±9)s,만기대조조위(82±26)s,만기HRT조위(48±18)s;유영행정:조기대조조(1 404 ±238)cm,조기HRT조(878±354)cm,만기대조조(2 411±818)cm,만기HRT조(1 310±434)cm;절경모형대서조、만기HRT조적도피잠복기급유영행정명현교조、만기대조조단(P<0.01).(2) Morris수미궁공간탐색실험:조기HRT조재목표상한유영정류시간위(34.0±3.0)s,교기타각조시간장(P<0.05).(3) MRI질자파보성상기술검측결과:NAA/Cr:조기대조조위1.12±0.17,조기HRT조1.26±0.12,만기대조조1.57±0.21,만기HRT조1.38±0.28,만기HRT조화만기대조조적NAA/Cr고우조기HRT조화조기대조조(F=6.05,P=0.040);조기HRT조여조기대조조、만기HRT조여만기대조조비교,차이무통계학의의(F=0.04,P=0.860).mI/Cr:조기대조조0.69±0.04,조기HRT조0.46±0.12,만기대조조0.70±0.03,만기HRT조0.75±0.08,만기HRT조、만기대조조여조기HRT조、조기대조조비교,차이유통계학의의(F=16.45,P=0.004),기중조기HRT조여조기대조조、만기HRT조여만기대조조조간차이명현(F =6.01,P=0.040),차실험간예적기시시간여시부HRT간예대mI/Cr존재교호작용(F=13.79,P=0.006),즉조기HRT가사mI/Cr비치강저.Cho/Cr:조기대조조0.95±0.09,조기HRT조0.80±0.12,만기대조조0.87±0.09,만기HRT조0.85±0.12,각조절경모형대서여신경세포막은태유관적Cho균무명현변화,각조간비교,차이무통계학의의(P>0.05).NAA/mI:실험간예적기시시간여시부HRT간예대NAA/mI존재교호작용(F=12.95,P=0.007),조기HRT가사NAA/mI비치승고,이만기결과칙상반.결론 HRT조기간예대개선절경모형대서적공간학습화기억력유적겁작용.
Objective To investigate the effect of estrogen replacement therapy applied in different periods to ovariectomized rats and to evaluate the cognitive function of the rats.Methods Totally 40 rats were ovariectomized to be postmenopausal models.They were divided into early hormone replacement therapy group (n =10,managed by estradiol valerate at day 3 after surgery),early control group (n =10,managed by saline at day 3 after surgery),late hormone replacement therapy (n =10,managed by estradiol valerate at day 90 after surgery for 30 days) and late control group (n =10,managed by saline at day 90 after surgery for 30 days).The behavior indicators of the rats were evaluated by Morris watermaze and hippocampal metabolite was detected by proton magnetic resonance spectroscopy,including N-acetylaspartate (NAA),choline containing compounds (Cho),creatine(Cr),myoinositol (mI),NAA/Cr,Cho/Cr and mI/Cr.Results (1) Navigation test: escape latency were (43 ± 13) s at the early control group,(28 ± 9) s at the early HRT group,(82 ±26) s at the late control group and (48 ± 18) s at late HRT group.Swimming distance were (1 404 ± 238) cm at the early control group,(878 ± 354) cm at the early HRT group,(2411 ±818) cm at the late control group and (1 310 ±434) cm at the late HRT group.The escape latency and swimming distance of the early and late HRT groups were significantly shorter than those at the control groups (P < 0.05).(2) Spatial probe test: the swimming time in the target quadrant of rats in the early HRT group (34.0 ± 3.0) s were longer than those in other groups (P < 0.05).(3) Proton magnetic resonance spectroscopy: NAA/Cr were 1.12 ±0.17 at the early control group,1.26 ±0.12 at the early HRT group,1.57 ±0.21 at the late control group and 1.38 ±0.28 at the late HRT group.The late HRT group and the late control group were higher than their early groups (F =6.05,P =0.040).There was no significant difference between the HRT groups and the control groups (F =0.04,P =0.860).mI/Cr were 0.69 ±0.04 at the early control group,0.46 ±0.12 at the early HRT group,0.70 ±0.03 at the late control group and 0.75 ± 0.08 at the late HRT group.There were statistically significant differences of the experimental time between the early and late groups(F =16.45,P =0.004).The differences between the early HRT group and the early control group,and the late HRT group and the late control group were significant(F =6.01,P =0.040).And there was an interaction with the experimental time and HRT measures (F =13.79,P =0.006) ; early HRT can reduce the average level of mI/Cr.Cho/Cr were 0.95 ± 0.09 at the early control group,0.80 ±0.12 at the early HRT group,0.87 ±0.09 at the late control group and 0.85 ± 0.12 at the late HRT group.There was no significant difference among those groups (P >0.05).NAA/mI: there was an interaction with the experimental time and HRT measures (F =12.95,P =0.007).Early HRT can elevated levels of NAA/mI,while the late results were reversed.Conclusion Earlier estrogen replacement therapy may play a positive role in improving cognitive function of the ovariectomized rats.