侧脑室注射干扰素-α对小鼠听皮层区听觉稳态反应的影响  

Effect of lateral ventricular injection of interferon-α on auditory steady-state response in auditory cortex of mice

作　　者：李英卓 陈婧玉 王帅[1] 秦岭[1] Li Yingzhuo;Chen Jingyu;Wang Shuai;Qin Ling(Department of Physiology,College of Life Sciences,China Medical University,Shenyang 110001,China)

机构地区：[1]中国医科大学生命科学学院生理教研室,沈阳110001

出　　处：《中华行为医学与脑科学杂志》2020年第6期494-498,共5页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金项目 (31671080)。

摘　　要：目的探讨脑室内注射干扰素α(interferon-α,IFN-α)对中枢神经细胞电活动的影响及相关机制。方法选取雄性昆明小鼠20只,在全麻下进行听皮层电极植入术及侧脑室埋管术。恢复1周后,所有小鼠随机分成IFN-α组(n=10)和生理盐水组(n=10),连续7 d通过侧脑室注射的方法分别给予IFN-α和生理盐水,记录给药前后的听皮层区听觉稳态反应(auditory steady-state response,ASSR)。记录结束后灌流取脑组织,采用免疫组化染色法观察海马区小胶质细胞和星形胶质细胞的变化。结果在给药前,生理盐水组和IFN-α组ASSR的平均强度差异无统计学意义[(3.49±0.56)dB,(3.22±0.87)dB;t=0.84,P=0.41]。给药后,IFN-α组ASSR的平均强度显著低于给药前[(3.22±0.87)dB,(1.59±0.44)dB;t=5.27,P<0.01],生理盐水组给予生理盐水前后ASSR差异无统计学意义[(3.49±0.56)dB,(3.46±0.61)dB;t=0.12,P=0.90]。免疫组织化学结果显示,IFN-α组海马CA1、CA3和DG区星形胶质细胞和小胶质细胞的密度高于生理盐水组,并伴有胶质细胞活化的形态改变。结论IFN-α可以诱发大脑海马区胶质细胞活化,并导致大脑皮层电生理活动的异常。ASSR能反映IFN-α诱导的脑功能异常,有可能是早期诊断的潜在指标。Objective To investigate the effect and mechanisms of lateral ventricular injection of interferon-alpha(IFN-α)on electrophysiological activity in central nervous system.Methods Twenty male Kunming mice were selected and subjected to auditory cortical electrode implantation and lateral ventricle intubation under general anesthesia.After one week of recovery,all mice were randomly divided into IFN-αgroup(n=10)and normal saline group(n=10).IFN-αand saline were administered by lateral ventricle injection for 7 consecutive days,and the auditory steady-state response(ASSR)in auditory cortex were recorded.Then the brain tissue was perfused,and the changes of microglia and astrocytes in the hippocampus were observed by immunohistochemical staining.Results There was no significant difference in the average intensity of ASSR between the saline group and the IFN-αgroup((3.22±0.87)dB vs(3.49±0.56)dB;t=0.84,P=0.41)before administration.After administration,the average intensity of ASSR in IFN-αgroup was significantly lower than that before administration((3.22±0.87)dB vs(1.59±0.44)dB,t=5.27,P<0.01),while the ASSR in saline group did not change before and after administration((3.49±0.56)dB,(3.46±0.61)dB;t=0.12,P=0.90).Immunohistochemistry revealed that the number of astrocytes and microglia in hippocampal CA1,CA3,and DG regions in the IFN-αgroup was higher than that of the saline group.Obvious morphological changes were also observed in the astrocytes and microglia.Conclusion IFN-αcan induce the activation of glial cells in the hippocampus and lead to the abnormal electrophysiological activity in the cortex.ASSR can reflect IFN-αinduced brain dysfunction,which may be a potential indicator for early diagnosis.

关 键 词：干扰素-Α 小胶质细胞 听皮层 脑电图 听觉稳态反应 小鼠 

分 类 号：R741.02[医药卫生—神经病学与精神病学]