CAJ | 학술논문

目的：检验由Stock等首次通过切除卵巢与切除嗅球所建立的动物模型是否适合作为一种女性更年期激越性抑郁症实验动物模型的可能性。方法将50只雌性SD大鼠随机分成5组（每组10只）：模型组、模型对照组、模型治疗组、假手术组、正常对照组。对前三组大鼠建立起双侧卵巢切除与双侧嗅球切除模型；对模型治疗组大鼠再联合应用氟西汀（10 mg/kg体质量）与戊酸雌二醇（100μg/kg体质量）进行干预，而对于模型对照组大鼠则用生理盐水进行处理，1次/d，连续21 d。但未对其他组大鼠作任何处理。应用旷场试验、强迫游泳试验、Morris水迷宫测试各组大鼠的行为与空间学习记忆变化。结果模型组或模型对照组大鼠较早出现严重的烦躁不安、易激怒、主动攻击、相互争斗状况；水平活动格子数与垂直向上爬行次数均明显增多，不动时间与逃避潜伏期均明显延长，而在原平台象限游泳时间、游泳穿过平台位置的次数则明显下降，这些指标与正常对照组或假手术组大鼠比较差异均有统计学意义（ P＜0.01）。然而，模型治疗组大鼠的以上指标则发生了与模型组或模型对照组大鼠完全相反的变化，与后两组之间相互比较差异均有统计学意义（P＜0.01），并接近于正常对照组或假手术组的水平，组间比较差异无统计学意义（P＞0.05）。结论本研究可重复Stock等的实验，其模型大鼠在病因、行为表现、学习记忆、药物显效时间及最终治疗效果等方面，能较好地模拟出在临床上女性更年期激越性抑郁症的发病及其外显症状的变化以及用药物干预的一般状况，也有相应的结构效度、表面效度和预测效度，故由本研究再现出Stock等的大鼠模型较适宜于作为一种女性更年期激越性抑郁症的实验动物模型，并有可能在后续进一步揭示相关临床特征与药物筛选等方面发挥出应有的潜力。目的：檢驗由Stock等首次通過切除卵巢與切除嗅毬所建立的動物模型是否適閤作為一種女性更年期激越性抑鬱癥實驗動物模型的可能性。方法將50隻雌性SD大鼠隨機分成5組（每組10隻）：模型組、模型對照組、模型治療組、假手術組、正常對照組。對前三組大鼠建立起雙側卵巢切除與雙側嗅毬切除模型；對模型治療組大鼠再聯閤應用氟西汀（10 mg/kg體質量）與戊痠雌二醇（100μg/kg體質量）進行榦預，而對于模型對照組大鼠則用生理鹽水進行處理，1次/d，連續21 d。但未對其他組大鼠作任何處理。應用曠場試驗、彊迫遊泳試驗、Morris水迷宮測試各組大鼠的行為與空間學習記憶變化。結果模型組或模型對照組大鼠較早齣現嚴重的煩躁不安、易激怒、主動攻擊、相互爭鬥狀況；水平活動格子數與垂直嚮上爬行次數均明顯增多，不動時間與逃避潛伏期均明顯延長，而在原平檯象限遊泳時間、遊泳穿過平檯位置的次數則明顯下降，這些指標與正常對照組或假手術組大鼠比較差異均有統計學意義（ P＜0.01）。然而，模型治療組大鼠的以上指標則髮生瞭與模型組或模型對照組大鼠完全相反的變化，與後兩組之間相互比較差異均有統計學意義（P＜0.01），併接近于正常對照組或假手術組的水平，組間比較差異無統計學意義（P＞0.05）。結論本研究可重複Stock等的實驗，其模型大鼠在病因、行為錶現、學習記憶、藥物顯效時間及最終治療效果等方麵，能較好地模擬齣在臨床上女性更年期激越性抑鬱癥的髮病及其外顯癥狀的變化以及用藥物榦預的一般狀況，也有相應的結構效度、錶麵效度和預測效度，故由本研究再現齣Stock等的大鼠模型較適宜于作為一種女性更年期激越性抑鬱癥的實驗動物模型，併有可能在後續進一步揭示相關臨床特徵與藥物篩選等方麵髮揮齣應有的潛力。
목적：검험유Stock등수차통과절제란소여절제후구소건립적동물모형시부괄합작위일충녀성경년기격월성억욱증실험동물모형적가능성。방법장50지자성SD대서수궤분성5조（매조10지）：모형조、모형대조조、모형치료조、가수술조、정상대조조。대전삼조대서건립기쌍측란소절제여쌍측후구절제모형；대모형치료조대서재연합응용불서정（10 mg/kg체질량）여무산자이순（100μg/kg체질량）진행간예，이대우모형대조조대서칙용생리염수진행처리，1차/d，련속21 d。단미대기타조대서작임하처리。응용광장시험、강박유영시험、Morris수미궁측시각조대서적행위여공간학습기억변화。결과모형조혹모형대조조대서교조출현엄중적번조불안、역격노、주동공격、상호쟁두상황；수평활동격자수여수직향상파행차수균명현증다，불동시간여도피잠복기균명현연장，이재원평태상한유영시간、유영천과평태위치적차수칙명현하강，저사지표여정상대조조혹가수술조대서비교차이균유통계학의의（ P＜0.01）。연이，모형치료조대서적이상지표칙발생료여모형조혹모형대조조대서완전상반적변화，여후량조지간상호비교차이균유통계학의의（P＜0.01），병접근우정상대조조혹가수술조적수평，조간비교차이무통계학의의（P＞0.05）。결론본연구가중복Stock등적실험，기모형대서재병인、행위표현、학습기억、약물현효시간급최종치료효과등방면，능교호지모의출재림상상녀성경년기격월성억욱증적발병급기외현증상적변화이급용약물간예적일반상황，야유상응적결구효도、표면효도화예측효도，고유본연구재현출Stock등적대서모형교괄의우작위일충녀성경년기격월성억욱증적실험동물모형，병유가능재후속진일보게시상관림상특정여약물사선등방면발휘출응유적잠력。
Objective To prove the possibility that ovariectomized ( OVX) and subsequently olfactory bul-bectomized(OBX) female rat pattern(OVX+OBX) first established by Stock et al in year 2000 is able to become a feasible animal model of agitated depression in menopausal women .Methods Fifty Sprague-Dawley adult female rats were randomly divided into five groups with ten rats per group:model,model control,model treatment,sham and intact. OVX and OBX were orderly performed on the first three group rats .Combined administration of fluoxetine (10 mg/kg, i.p.) and estradiol (100 μg/kg, s.c.) was given to rats in model treatment group after fourteen days of OBX ,while saline solution was administered to rats in model control group ,and the above daily interventions were conducted for a period of twenty-one consecutive days;while the remaining group rats were not treated at all .Open field test ,forced swimming test and Morris water maze were utilized to detect behavioral changes of rats in all groups .Results Rats in model or model control group showed early-onset and severe irritation ,agitation ,active attacks and fights or biting with each other .Meanwhile , the crossing score , rearing score , immobility time and escape latency in the above two group rats were the highest or the longest ,while the time rat swimming in the quadrant originally put a platform and the number of rat swimming through a fixed position for putting the platform became the shortest or the smallest .All these changes had a statistically significant difference in comparison with those in sham or intact group rats ( P<0.01 ) . However ,changes of the above parameters in model treatment rats became just opposite to those in model or model control group rats with a statistically significant difference ( P<0.01 ) , and were also near the levels of related param-eters in sham group or intact group rats with no statistically significant differences ( P >0.05 ) .Conclusion Our study can fully replicates the results , including OVX+OBX female rat model designed by Stock et al , and the behav-ioral changes ,surgical causes and antidepressant treatment efficacies showed from OVX +OBX rat model in this stud-y, which are very similar to the correspondent results clinically found in an agitated depression of menopausal women , and also share relative surface validity , construct validity and predictive validity , thereby indicating that the female rat OVX+OBX operational pattern has a strong potential to become a feasible agitated depression animal model of menopausal female patients .