大鼠创伤后应激障碍模型及腹腔注射干预的影响

Developing rat models for post-traumatic stress disorder and observation on the outcomes intervened by intraperitoneal injection

目的:制备大鼠条件性恐惧记忆的创伤后应激障碍(PTSD)模型,并观察腹腔注射(ip)生理盐水干预的影响。方法:对大鼠进行连续3 d"声音-电击"配对刺激,24 h后检测木僵时间作为观察条件性恐惧记忆的指标,按木僵时间百分比分层随机抽取模型大鼠14只均分为对照组和生理盐水组,对后一组进行ip生理盐水(qd)2周干预,干预后第2 d、4 d、8 d、15 d进行木僵时间检测,随后进行连续7 d的Morris水迷宫检测。结果:对38只大鼠进行"声音-电击"刺激后,其木僵时间百分比由刺激前(18.63±9.76)%增至(59.01±20.44)%(配对t检验,P<0.01),且木僵时间百分比与体质量成正相关(r=0.4200,P<0.01),其中有28只大鼠的木僵时间百分比≥50%。木僵时间检测显示对照组模型有一定稳定性(单因素ANOVA,P>0.05),而生理盐水组不仅检测日间差异有显著性意义(单因素ANOVA,P<0.01),且可促进模型动物恐惧记忆的消退(重复测量双因素ANOVA,测试次间P<0.01,处理组间P<0.05)。定位航行实验的逃避潜伏期和空间探索实验的穿台次数检测表明两组差异均P>0.05。结论:"声音-电击"配对刺激可形成比较稳定的条件性恐惧记忆而制备PTSD模型,ip干预可促进其条件性恐惧记忆的消退。

Objective：To establish rat models of post-traumatic stress disorder（PTSD） mimicked by conditioned fear memory and observe the impacts of intervention via intraperitoneal injection（ip） of saline.Methods：A protocol of 3-day ＂sound-electric shock＂ paired stimulation was introduced to preparing the rat model of PTSD.By stratified random sampling,the model rats were evenly divided into control group and saline group（n=7）,according to the percentage of freezing time representing conditioned fear memory.During 2-week intervention（ip,qd） of rats in saline group,the freezing time of model rats in 2 groups on the day 2,4,8 and 15 was measured,and then Morris water maze test was performed in a 7-day period.Results：After 3-day paired stimulation,the percentage of freezing time of 38 rats [（18.63 ± 9.76）%] was increased to（59.01±20.44）%（paired t test,P0.01） including 28 rats with percentage of freezing time≥ 50%,and was observed to correlate with the body weight（r=0.4200,P0.01）.A one-way ANOVA of freezing time data of model rats in control group showed that the rat model had a certain stability（P0.05）,but in saline group presented a significant difference（P0.01）.Moreover,a repeated measurement of two-way ANOVA of freezing time data indicated an intervention of ip promoted the extinction of fear memory in the model rats（P0.05）,yet that of Morris water maze test data showed no significant difference（P0.05） between two groups.Conclusion：A stable rat model for PTSD with conditioned fear memory may be developed using a protocol of ＂sound-electric shock＂ paired stimulation,and an intervention of ip may promote its extinction of conditioned fear memory.