氟西汀与艾司西酞普兰对大鼠抑郁样行为及海马BDNF基因表达的影响

Effects of fluoxetine and escitalopram on depressive-like behavior and hippocampal BDNF gene expression in adult rats

目的考察氟西汀及艾司西酞普兰不同的使用时程对大鼠抑郁样行为及海马脑源性神经营养因子（brainderivedneurotrophicfactor，BDNF）表达水平的影响。方法96只sD大鼠采用随机数字表法随机分为12组，每组8只：（1）M1组：正常对照1周；（2）M2组：CUMS＋生理盐水1周；（3）M3组：CUMS＋氟西汀1周；（4）M4组：CUMS＋艾司西酞普兰1周；（5）M5组：正常对照2周；（6）M6组：CUMS＋生理盐水2周；（7）M7：CUMS＋氟西汀2周；（8）M8组：CUMS＋艾司西酞普兰2周；（9）M9组：正常对照3周；（10）M10组：CUMS＋生理盐水3周；（11）M11组：CUMS＋氟西汀3周；（12）M12组：CUMS＋艾司西酞普兰3周。造模后M2、M6、MIO组大鼠腹腔注射生理盐水，M3、M7、M11组大鼠腹腔注射氟西汀，M4、M8、M12组大鼠腹腔注射艾司西酞普兰。1周后，M1、M2、M3、M4组大鼠行旷场实验及糖水偏好实验，实时荧光定量PCR方法检测BDNF基因表达。2周后，M5、M6、M7、M8组行相同操作。3周后，M9、M10、M11、M12组行相同操作。结果在旷场实验中，M1组[（3925．70±322．32）cm]与M3组[（1841．85±786．33）cm]，M6组[（1820．31±296．00）cm]与M8组[（4002．72±1447．19）cm]，M10组[（1961．66±919．16）cm]与M11组[（3741．72±1064．46）cm]、M10组[（1961．66±919．16）cm]与M12组[（4280．43±1187．05）cm]间10min总行程差异有统计学意义（P〈0．05）。在糖水偏好实验中，M2组[（56．23±7．49）％]与M4组[（70．55±4．96）％]，M6组[（60．22±8．81）％]与M8组[（75．08±4．15）％]，M10组[（60．26±7．20）％]与M11组[（73．88±7．73）％]、M10组[（60．26±7．20）％]与M12组[（73．52±7．58）％]间糖水偏好率差异有统计学意义（P〈0．05）。M2组（0．66±0．14）与M4组（1．15-0．20），M10组（0．90±0．15）与M11组（1．22±0．09）、M10组（0．90±0．15）与M12组（1．48±0．20）间BDNF基因相对表达量差异有统计学意义（P〈0．05）。结论氟西汀与艾司西酞普兰使用3周后均能改善大鼠抑郁样行为，并提高海马中BDNFmRNA的表达。艾司西酞普兰在治疗抑郁症方面起效时间更快，可能与BDNFmRNA的表达快速增高有关。

Objective To investigate the effects of different duration of fluoxetine and escitalopram ad- ministration on depressive-like behavior and hippoeampal BDNF expression in adult rats. Methods Ninety-six SD rats were randomly divided into twelve groups ： （ 1 ） M1 group ： normal control for one week, （2） M2 group ： CUMS ＋saline for one week, （3） M3 group ： CUMS＋fluoxetine for one week, （4） M4 group ： CUMS＋escitalopram for one week, （5） M5 group ： normal control for two weeks, （6） M6 group ： CUMS ＋ saline for two weeks, （ 7 ） M7 group ： CUMS＋fluoxetine for two weeks, （8）M8 group： CUMS＋escitalopram for two weeks, （9）M9 group： normal control for three weeks, （10） M10 group： CUMS＋saline for three weeks, （ 11 ） Mll group： CUMS＋fluoxetine for three weeks, （12） M8 group： CUMS＋escitalopram for three weeks. After CUMS procedures,rats in M2 group, M6 group and M10 group were injected with saline, M3 group, M7 group and Mll group were injeeted with fluoxetine, and rats in M4 group,M8 group,M12 group were injected with escitalopram. After one week of intervention,the openfield test and 1% sucrose preference test were performed to evaluate depression-like behaviors in rats of M1 group, M2 group, M3 group and M4 group. After behavior test, rats were sacrificed and the hippocampi were isolated. The expression of BDNFmRNA was detected by using real-time quantitative PCR. After two weeks of intervention,rats in M5 group, M6 group, M7 group and M8 group underwent the same behavioral. After three weeks of intervention, rats in M9 group, M10 group, M ll group and M12 group underwent the same behavioral test. Results In the open-field test,total distance travelled in 10 minutes was significant difference among the following groups： M1 groun （ （3925.70±322.323 era） vs group （ （1841.85±786.33） em） ,M6 group （ （1820.31±296.00） em） vsM8 group （（4002.72±1447.19） cm） ,MIO （ （1961.66±919.16） era） group vs M11 group （（3741.72±1064.46） cm） ,MIO group （ （1961.66±919.16） cm） vs M12 group （（4280.43±1187.05） cm）.In the 1% sucrose preference test, the difference of sucrose preference consumption was statistically significant （P〈 0. 05 ） among the following groups： M2 group （（56.23±7.49）%） vs M4 group （（70.55±4.96）%） ,M6 group （（60.22±8.81）%） vs M8 group （（75.08±4.15）%）,MIO group （（60.26±7.20）%） vs Mll group （（73.88±7.73）%）,MIO group （（60.26 ± 7.20） % ） vs M 12 group （ （ 73.52 ± 7.58 ） % ）. The expression level of BDNF was significant difference among these groups： M2 group （0.66±0.14） vs M4 group （1.15±0.20） ,M10 group （0.90±0.15） vs Mll group （ 1.22± 0.09） ,M10 group （0.90±0.15） vs M12 group （1.48±0.20）. Conelusioia Both of fluoxetine and escitalopram can improve depression-like behaviors in rats and significantly increase the expression of the hippoeampal BDNFmRNA. Compared with fluoxetine, escitalopram has a shorter onset time in the treatment of depression. It may be related with a rapid increase of the expression of BDNF mRNA.