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[雌激素替代疗法对去卵巢大鼠认知功能的影响]

[Effects of estrogen replacement therapy on cognitive function of ovariectomized rats].

作者信息

Liu Xiaoyan, Wang Liping, Peng Danhong, Wang Yan, Ren Mulan

机构信息

Department of Obstetrics and Gynecology,Zhongda Hospital, Southeast University, Nanjing 210009, China.

Department of Obstetrics and Gynecology,Zhongda Hospital, Southeast University, Nanjing 210009, China. Email:

出版信息

Zhonghua Fu Chan Ke Za Zhi. 2014 Jan;49(1):42-7.

Abstract

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, (2 411 ± 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.

摘要

目的

探讨不同时期应用雌激素替代疗法对去卵巢大鼠的影响,并评估大鼠的认知功能。

方法

将40只大鼠去卵巢制成绝经后模型。分为早期激素替代治疗组(n = 10,术后第3天给予戊酸雌二醇)、早期对照组(n = 10,术后第3天给予生理盐水)、晚期激素替代治疗组(n = 10,术后第90天给予戊酸雌二醇,持续30天)和晚期对照组(n = 10,术后第90天给予生理盐水,持续30天)。采用Morris水迷宫评估大鼠行为学指标,用质子磁共振波谱检测海马代谢物,包括N - 乙酰天门冬氨酸(NAA)、含胆碱化合物(Cho)、肌酸(Cr)、肌醇(mI)、NAA/Cr、Cho/Cr和mI/Cr。

结果

(1)定位航行实验:早期对照组逃避潜伏期为(43 ± 13)s,早期激素替代治疗组为(28 ± 9)s,晚期对照组为(82 ± 26)s,晚期激素替代治疗组为(48 ± 18)s。早期对照组游泳距离为(1 404 ± 238)cm,早期激素替代治疗组为(878 ± 354)cm,晚期对照组为(2 411 ± 818)cm,晚期激素替代治疗组为(1 310 ± 434)cm。早期和晚期激素替代治疗组的逃避潜伏期和游泳距离均显著短于对照组(P < 0.05)。(2)空间探索实验:早期激素替代治疗组大鼠在目标象限的游泳时间为(34.0 ± 3.0)s,长于其他组(P < 0.05)。(3)质子磁共振波谱:早期对照组NAA/Cr为1.12 ± 0.17,早期激素替代治疗组为1.26 ± 0.12,晚期对照组为1.57 ± 0.21,晚期激素替代治疗组为1.38 ± 0.28。晚期激素替代治疗组和晚期对照组高于各自早期组(F = 6.05,P = 0.040)。激素替代治疗组与对照组之间无显著差异(F = 0.04,P = 0.860)。早期对照组mI/Cr为0.69 ± 0.04,早期激素替代治疗组为0.46 ± 0.12,晚期对照组为0.70 ± 0.03,晚期激素替代治疗组为0.75 ± 0.08。早期和晚期组间实验时间有统计学差异(F = 16.45,P = 0.004)。早期激素替代治疗组与早期对照组、晚期激素替代治疗组与晚期对照组之间差异显著(F = 6.01,P = 0.040)。且实验时间与激素替代治疗措施存在交互作用(F = 13.79,P = 0.006);早期激素替代治疗可降低mI/Cr平均水平。早期对照组Cho/Cr为0.95 ± 0.09,早期激素替代治疗组为0.80 ± 0.12,晚期对照组为0.87 ± 0.09,晚期激素替代治疗组为0.85 ± 0.12。各组间无显著差异(P > 0.05)。NAA/mI:实验时间与激素替代治疗措施存在交互作用(F = 12.95,P = 0.007)。早期激素替代治疗可提高NAA/mI水平,而晚期结果相反。

结论

早期雌激素替代疗法可能对改善去卵巢大鼠的认知功能起积极作用。

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