组蛋白去乙酰化酶在孕鼠孕期免疫激活所致子代青春期感觉门控损伤中的作用  

Role of histone deacetylase in the sensory gating impairment of offspring during puberty caused by immune activation in pregnant rats

作　　者：王冠玉 刘森淇 杨勇锋[1,2] 李文强 吕路线[1,2] 苏玺 WANG Guanyu;LIU Senqi;YANG Yongfeng;LI Wenqiang;LYU Luxian;SU Xi(Key Laboratory of the Second Affiliated Hospital of Xinxiang Medical University,Xinxiang 453002,Henan Province,China;Henan Key Laboratory of Biological Psychiatry,Xinxiang 453002,Henan Province,China)

机构地区：[1]新乡医学院第二附属医院重点实验室,河南新乡453002 [2]河南省生物精神病学重点实验室,河南新乡453002

出　　处：《新乡医学院学报》2024年第2期101-108,共8页Journal of Xinxiang Medical University

基　　金：国家自然科学基金资助项目(编号:82001407,81971252,82171498);河南省重大科技专项(编号:201300310200);河南省科技攻关项目(编号:222102310130);河南省卫生健康委医学科技攻关省部共建青年项目(编号:SBGJ202103094);河南省医学科技攻关项目(编号:2018020371);新乡市科技厅科技攻关项目(编号:GG2021035)。

摘　　要：目的探讨各亚型组蛋白去乙酰化酶(HDAC)在母孕期免疫激活子代大鼠额叶、海马及肝脏组织中的表达及其与前脉冲抑制效率(PPI%)的相关性。方法将受孕成功的10只Sprague-Dawley雌鼠随机分为模型组(n=5)和对照组(n=5)。于妊娠期第9天,模型组孕鼠经尾静脉注射10 mg·kg^(-1)聚肌胞苷酸(Poly I:C),对照组孕鼠给予等体积无菌生理盐水。3 h后,尾静脉取血,采用酶联免疫吸附法检测2组孕鼠血浆中白细胞介素(IL)-1β、IL-6和肿瘤坏死因子-α(TNF-α)水平来评估孕鼠免疫激活状态。将2组孕鼠饲养至自然生产,子鼠在出生后第21天断乳,选取雄性后代继续饲养。在子代大鼠青春期(即出生后第40天)时进行前脉冲抑制测试,评估其空间识别记忆和感觉门控功能。采用实时荧光定量聚合酶链式反应检测2组子代大鼠海马、额叶及肝脏组织中HDAC家族的基因表达水平。结果模型组孕鼠血浆中IL-6、IL-1β、TNF-α表达水平显著高于对照组(P<0.05)。在前脉冲刺激为75 dB时,模型组子代青春期大鼠的PPI%显著低于对照组(P<0.05);前脉冲刺激为80、85 dB时,模型组与对照组子代青春期大鼠的PPI%比较差异无统计学意义(P>0.05)。在额叶组织中,模型组子代大鼠HDAC3、HDAC4、HDAC8、HDAC9、HDAC10、Sirt mRNA表达水平显著低于对照组子代大鼠(P<0.05),HDAC5 mRNA表达水平显著高于对照组子代大鼠(P<0.05);模型组与对照组子代大鼠HDAC1、HDAC2、HDAC6、HDAC7、HDAC11 mRNA表达水平比较差异无统计学意义(P>0.05)。在海马组织中,模型组子代大鼠HDAC1、HDAC8、HDAC10 mRNA表达水平显著低于对照组子代大鼠(P<0.05),HDAC2、HDAC5 mRNA表达水平显著高于对照组子代大鼠(P<0.05);模型组与对照组子代大鼠HDAC3、HDAC4、HDAC6、HDAC7、HDAC9、HDAC11、Sirt mRNA表达水平比较差异无统计学意义(P>0.05)。在肝脏组织中,模型组子代大鼠HDAC6、HDAC10 mRNA表达水平显著低于对照组子代Objective To investigate the expression of histone deacetylase(HDAC)isoforms in the frontal lobe,hippocampus and liver of offspring rats delivered by rats with maternal immune activation and their correlation with the efficiency of prepulse inhibition(PPI%).Methods Ten pregnant Sprague-Dawley rats were randomly divided into the model group(n=5)and control group(n=5).The rats in the model group were injected with 10 mg·kg^(-1) polyinosinic-polycytidylic acid(Poly I:C)via the caudal vein on the 9 th day of pregnancy,while rats in the control group were given the same volume of sterile physiological saline.After 3 h,blood was collected from the caudal vein,and the levels of interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)in the plasma of pregnant rats were detected by enzyme-linked immunosorbent assay to evaluate the immune activation status.The pregnant rats in the two groups were fed until natural delivery,the offspring rats were weaned on the 21 st day after birth,and the male offspring rats were fed continuously.A prepulse inhibition test was performed at puberty(the 40 th day after birth)to evaluate the spatial recognition memory and sensory gating function of the offspring rats.The expression levels of the HDAC gene family in the hippocampus,frontal lobe and liver of offspring rats were detected by real-time fluorescence quantitative polymerase chain reaction.Results The plasma IL-6,IL-1βand TNF-αlevels in the model group were significantly higher than those in the control group(P<0.05).When the prepulse stimulation was 75 dB,the PPI%of the offspring rats at puberty in the model group was significantly lower than that in the control group(P<0.05).When the prepulse stimulation was 80 and 85 dB,there was no significant difference in PPI%between the model group and the control group(P>0.05).In the frontal lobe,the expression levels of HDAC3,HDAC4,HDAC8,HDAC9,HDAC10 and Sirt mRNA in the offspring rats in the model group were significantly lower than those in the control group(P<0.05),while the expr

关 键 词：孕期感染 精神分裂症 感觉门控损伤 组蛋白去乙酰化酶 

分 类 号：R749.302[医药卫生—神经病学与精神病学]