CAJ | 학술논문

目的观察雌二醇替代治疗对去卵巢大鼠新事物探索和恐惧记忆消退等认知功能的影响.方法 60只成年雌性大鼠(＞ 90d,250 ～ 300g)双侧卵巢切除手术后,根据不同剂量和给药时间通过皮下注射进行雌二醇替代治疗,手术后第2天治疗组分为低剂量治疗组(OVX+ LD,0.1 mg· kg-1)、中剂量治疗组(OVX+ MD,0.3 mg·kg-1)、高剂量治疗组(OVX+ HD,0.9 mg·kg-1),手术后不同时间分为2周后中剂量治疗组(MD+2W)和4周后中剂量治疗组(MD+4W)以及手术组(OVX)和假手术组(SH).给药维持1月后用新事物探索和恐惧记忆消退的方法进行认知功能的测定.结果 (1) OVX组[(5.83±4.5)s]新事物探索能力较SH组[(27.14±6.6)s]明显降低,差异有统计学意义(P＜0.01)；雌二醇替代治疗(除HD组)呈一定剂量和时间效应提升大鼠新事物探索能力,且MD[(27.86±2.6)s]组较OVX组有统计学差异(P＜0.05)；LD组、MD+2W组较OVX组新事物探索能力有所提升,但差异并无统计学意义(P＞0.05).(2) OVX组[(21.67±2.0)％]其恐惧度较SH组[(56.81±4.6)％]明显降低,差异有统计学意义(P＜0.01)；LD组、MD组和MD+2W组较OVX组均可显著提升大鼠恐惧度(P＜0.01),但HD组对恐惧记忆的能力减弱,MD+4W组较OVX组无明显变化(P＞0.05).(3)OVX组较SH组其恐惧记忆消退速度明显下降(P＜0.01)；雌二醇替代治疗(除MD+ 4W组)均可一定程度的提升大鼠恐惧消退的速度(P＜0.01).结论雌二醇能改善情绪和抑制性学习记忆,并提示早期给予雌激素治疗改善认知功能更好.
목적 관찰자이순체대치료대거란소대서신사물탐색화공구기억소퇴등인지공능적영향.방법 60지성년자성대서(＞ 90d,250 ～ 300g)쌍측란소절제수술후,근거불동제량화급약시간통과피하주사진행자이순체대치료,수술후제2천치료조분위저제량치료조(OVX+ LD,0.1 mg· kg-1)、중제량치료조(OVX+ MD,0.3 mg·kg-1)、고제량치료조(OVX+ HD,0.9 mg·kg-1),수술후불동시간분위2주후중제량치료조(MD+2W)화4주후중제량치료조(MD+4W)이급수술조(OVX)화가수술조(SH).급약유지1월후용신사물탐색화공구기억소퇴적방법진행인지공능적측정.결과 (1) OVX조[(5.83±4.5)s]신사물탐색능력교SH조[(27.14±6.6)s]명현강저,차이유통계학의의(P＜0.01)；자이순체대치료(제HD조)정일정제량화시간효응제승대서신사물탐색능력,차MD[(27.86±2.6)s]조교OVX조유통계학차이(P＜0.05)；LD조、MD+2W조교OVX조신사물탐색능력유소제승,단차이병무통계학의의(P＞0.05).(2) OVX조[(21.67±2.0)％]기공구도교SH조[(56.81±4.6)％]명현강저,차이유통계학의의(P＜0.01)；LD조、MD조화MD+2W조교OVX조균가현저제승대서공구도(P＜0.01),단HD조대공구기억적능력감약,MD+4W조교OVX조무명현변화(P＞0.05).(3)OVX조교SH조기공구기억소퇴속도명현하강(P＜0.01)；자이순체대치료(제MD+ 4W조)균가일정정도적제승대서공구소퇴적속도(P＜0.01).결론 자이순능개선정서화억제성학습기억,병제시조기급여자격소치료개선인지공능경호.
Objective To investigate the effects of estradiol replacement therapy on novel-object recognition and extinction of conditioned fear memory in ovariectomized (OVX) rats.Methods Sixty sexually mature (＞90 days) female SD rats weighing 250g-300g were used as subjects.The rats were randomly divided into 7groups as following:OVX with low dose of estradiol replacement (OVX + LD,0.1 mg · kg-1),medium dose (OVX + MD,0.3mg · kg-1) and high dose (OVX + HD,0.9mg · kg-1),estradiol replacement with medium dose at 2 weeks after OVX (MD + 2W) and 4 weeks after OVX (MD + 4W),OVX group and Sham group (SH).According to the different dose and time schedules,each group was administrated estradiol or vehicle via subcutaneous injection on the dorsal side of the rat.Estradiol maintained for one month after the surgery,and then the novel-object recognition and extinction of conditioned fear memory were tested.Results (1) The rats after OVX (5.83 ±4.5)s showed access-dependent impairments on novel-object recognition ((5.83 ± 4.5)s vs(27.14 ± 6.6)s,P ＜0.01) and the estradiol replacement therapy can reverse this impairment,but not in the HD group.There was an increase of the ability on novel-object recognition in group LD and MD + 2W as compared with group OVX,but the difference was not statistically significant (P ＞ 0.05).Moreover,group MD (27.86 ± 2.6)s had a significant difference compared with group OVX (P ＜ 0.05).(2) The conditioned fear memory of rats after OVX (21.67 ± 2.0) ％showed significantly lower than group SH (56.81 ± 4.6) ％ (P ＜ 0.01).Chronic administration with estradiol enhanced acquisition of context fear,respectively (P ＜ 0.01),but except group HD and group MD + 4W.The group HD(18.43 ± 1.1)％ was negatively enhanced and the group MD +4W(25.25 ±2.5)％ was no difference compared with group OVX.(3) On extinction of conditioned fear memory,the OVX rats produced significantly less freezing by fear context (F =3.337,P ＜ 0.01),and estradiol treatment (except group MD + 4W)also facilitated the extinction of conditioned fear memory,respectively (P ＜ 0.01).Conclusion These results demonstrate that estradiol may have a beneficial effect on the cognition function,and the improving effect is better when estradiol replacement is given at once depriving of sex hormone.