目的探讨癫癎伴发抑郁(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、癫癎组、慢性温和应激刺激(chronic mild stress,CMS)组、癫癎+CMS组。癫癎组采用锂-匹罗卡品进行慢性癫造模,CMS组采用CMS进行抑郁造模,癫癎+CMS组在进行慢性癫癎造模后再予以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,癫癎组(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),癫癎+CMS组则降低得更为明显,差异有统计学意义(P〈0.01);与癫癎组比较,癫癎+CMS组各指标降低,差异有统计学意义(P〈0.05);与CMS组比较,癫癎+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,癫癎组、CMS组、癫癎+CMS组降低,差异有统计学意义(P〈0.05),癫癎+CMS组降低得更为明显;与癫癎组比较,癫癎+CMS组5-HT1A受体mRNA表达差异无统计学意义;与CMS组比较,癫癎+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-匹罗卡品慢性癫癎造模后结合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.