癫伴发抑郁大鼠模型建立及评价

Establishment and Assessment of Rat Model in Epilepsy with Depression

目的探讨癫伴发抑郁(epilepsy with depression,EWD)大鼠模型建立的可行性和有效性。方法通过测定蔗糖水消耗和旷场试验基线值,选择行为学相近的SD大鼠,随机分为正常组、癫组、慢性温和应激刺激(chronic mild stress,CMS)组、癫+CMS组。癫组采用锂-匹罗卡品进行慢性癫造模,CMS组采用CMS进行抑郁造模,癫+CMS组在进行慢性癫造模后再予以CMS进行联合造模以制备EWD大鼠模型。最终32只大鼠纳入统计,每组8只。通过旷场试验和糖水消耗试验观察大鼠自发性行为改变,实时聚合酶链式反应(real time polymerase chain reaction,RTPCR)检测海马区5-羟色胺1A(5-hydroxy tryptamine 1A,5-HT1A)受体mRNA表达的变化。结果大鼠的抑郁行为学指标与正常组比较,癫组(糖水消耗、糖水偏爱、垂直及水平运动次数)差异无统计学意义,CMS组各指标降低,差异有统计学意义(P<0.05),癫+CMS组则降低得更为明显,差异有统计学意义(P<0.01);与癫组比较,癫+CMS组各指标降低,差异有统计学意义(P<0.05);与CMS组比较,癫+CMS组的糖水偏爱程度降低,差异有统计学意义(P<0.05)。大鼠的5-HT1A受体mRNA表达与正常组比较,癫组、CMS组、癫+CMS组降低,差异有统计学意义(P<0.05),癫+CMS组降低得更为明显;与癫组比较,癫+CMS组5-HT1A受体mRNA表达差异无统计学意义;与CMS组比较,癫+CMS组5-HT1A受体mRNA表达降低,差异有统计学意义(P<0.05)。结论大鼠经锂-匹罗卡品慢性癫造模后结合CMS,可为EWD的实验及临床研究提供较为理想的动物模型。

Objective To explore the feasibility and validity of the model of epilepsy with depression（EWD）. Methods After detecting baseline values by the open-field test and the saccharose water consumption test, SD rats with similar behavior were divided into4 groups： normal group, epilepsy group, CMS group, and epilepsy with CMS group.Epilepsy group received lithium-pilocarpine to establish chronic epilepsy model. CMS group was exposed to CMS to establish depression model. EWD model was established when given CMS after chronic pilocarpine-induced epileptic rats. Finally 32 SD rats were included in the statistics（n=8）. The open-field test and the saccharose water consumption test were performed to assess depression-like behaviour. The expression of 5-HT1 A receptor mRNA in hippocampus was detected by the RT-PCR method. Results Compared with the normal group, all the behavioral data of depression, including consumption and preference of saccharose water,locomotion times in open-field test, decreased in the CMS group（P〈0.05）, especially in the epilepsy＋CMS group（P〈0.01）, which had statistical significance. Compared with the epilepsy group, all the data decreased in the epilepsy＋CMS group, which had statistical significance（P〈0.05）. Compared with the CMS group, the preference of saccharose water decreased in the epilepsy＋CMS group, which had statistical significance（P〈0.05）.Compared with the normal group, the expression of 5-HT1 A receptor mRNA decreased in the other three groups, especially in the epilepsy＋CMS group, which had statistical significance（P〈0.05）. Compared with the epilepsy group, the expression of 5-HT1 A receptor mRNA had no statistical significance in the epilepsy＋CMS group. Compared with the CMS group, the expression of 5-HT1 A receptor mRNA decreased in the epilepsy＋CMS group, which had statistical significance（P〈0.05）. Conclusion CMS after chronic pilocarpine-induced epileptic rats could ideally produce EWD rat model for clinical research.