摘要目的 探讨丘脑前核(ANT)电刺激对颞叶癫痫猴海马神经元的神经保护作用.方法 将8只雄性恒河猴随机分为模型对照组(简称对照组)、假刺激组以及刺激组,采用左侧海马注射海人酸的方法建立颞叶癫痫猴模型.比较各组的癫痫发作频率.造模后6个月采用HE染色及NeuN染色观察海马组织的病理损伤及纤维化情况,以Western blot方法定量分析海马组织中热休克蛋白-70(HSP-70)、NeuN及Caspase-3蛋白的表达.结果 所有接受海人酸注射的动物均出现癫痫发作,刺激组总发作次数为(11.2±2.3)次,较假刺激组[(21.0±4.8)次]降低42.8％ (P ＜0.05).刺激组月平均发作频率为(3.7±0.8)次,较假刺激组[(7.0±3.7)次]降低45.7％ (P ＜0.05).刺激组海马存活神经元数量[(14.6±3.9)个/100 μm2)]明显大于假刺激组[(8.4±3.3)个/100 μm2](P＜0.05),而纤维化程度较假刺激组明显降低.假刺激组的HSP-70含量明显高于对照组(P＜0.01),但与刺激组之间的差异无统计学意义(P＞0.05);假刺激组的NeuN含量显著低于对照组和刺激组(P＜0.01,P＜0.05),而Caspase-3含量显著高于对照组和刺激组(P＜0.01,P＜0.05).结论 长期进行ANT电刺激可减轻颞叶癫痫猴海马神经元的损伤及纤维化,这可能是ANT电刺激治疗颞叶癫痫的重要机制.

abstractsObjective To investigate the neuroprotective effects of anterior thalamic nuclei (ANT) stimulation on hippocampal neurons in epileptic monkeys.Methods Eight male rhesus monkeys were randomly assigned to a model control group,a sham-stimulation group,and a stimulation group.A monkey model of temporal lobe epilepsy was induced by injection of kainic acid in the left hippocampus.The seizure frequency was compared in each group.At 6 months after modeling,immunohistochemical method was used to observe the pathological injury and fibrosis in hippocampal tissue.Western blot was used to quantitatively analyze the contents of heat shock protein-70 (HSP-70),NeuN,and caspase-3 in hippocampal tissue.Results All animals that received the kainic acid injections had seizures.The total number of seizures in the stimulation group was 11.2 ± 2.3 times,compared with 21.0 ± 4.8 times in the sham-stimulation group,it decreased 42.8％ (P ＜0.05).The monthly seizure frequency in stimulation group was 3.7 ±0.8 times.compared with 7.0 ± 3.7 times in the sham-stimulation group,it deceased 45.7％ (P ＜ 0.05).The number of surviving neurons in the hippocampi of the animals of the ANT stimulation group [(14.6 ± 3.9)/100 μm2] was significantly higher than that of the sham-stimulation group [(8.4 ± 3.3)/100 μm2] (P ＜0.05).Compared with the sham-stimulation group,the degree of fibrosis was reduced significantly.The content of HSP-70 in the sham stimulation group was significantly higher than that of the control group (P ＜0.01),but there was no significant difference between the stimulation groups (P ＞ 0.05).The content of NeuN in sham-stimulation group was significantly lower than that in the control group and the stimulation group (P ＜ 0.01,P ＜ 0.05).The content of Caspase-3 in sham-stimulation group was significantly higher than that in the control group and the stimulation group (P ＜ 0.01,P ＜ 0.05).Conclusions Long-term ANT stimulation may reduce the hippocampal injury and gliosis in temporal lobe epilepsy monkeys.This may be an important mechanism of ANT stimulation for the treatment of temporal lobe epilepsy.