针对切除卵巢与嗅球的大鼠可能成为一种女性更年期激越性抑郁症实验动物模型的印证研究

Operational pattern of ovariectomy and subsequent olfactory bulbectomy orderly performed on female rats may be an agitated depression animal model of menopausal women

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。

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 txg/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 cbanges 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 grouprats 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, constnlct 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.