奥氮平对精神分裂症神经发育模型小鼠前脉冲抑制的影响  

Effects of olanzapine treatment on prepulse inhibition in neurodevelopmental mice model of schizophrenia

作　　者：陈升东 江坤鸿 牛威 朱晓丽 周蕾 张理义 孔令明 徐亚金 Chen Shengdong;Jiang Kunhong;Niu Wei;Zhu Xiaoli;Zhou Lei;Zhang Liyi;Kong Lingming;Xu Yajin(Department of Neurology,Changzhou Medical District,No.904 Hospital of Joint Logistics Support Force,Changzhou 213003,China;Treatment Institution,No.904 Hospital of Joint Logistics Support Force,Changzhou 213003,China;Medical Aderministrition,Taijiang Hospital of Sanming,Sanming 365001,China)

机构地区：[1]联勤保障部队第904医院常州医疗区神经内科,常州213003 [2]联勤保障部队第904医院全军心理疾病防治中心,常州213003 [3]三明市台江医院医务科,三明365001

出　　处：《中华行为医学与脑科学杂志》2022年第2期116-121,共6页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：东部战区医学科技创新重点课题(15ZD010)。

摘　　要：目的构建前脉冲抑制(prepulse inhibition,PPI)损伤的精神分裂症神经发育小鼠模型,并探讨奥氮平(olanzapine,OLZ)干预对PPI功能的影响。方法SPF级C57BL/6孕9 d母鼠尾静脉注射聚肌苷酸-聚胞苷酸[polyinosinic acid-polycytidilicacid,Poly(I∶C)](6 mg/kg)进行免疫刺激,子代小鼠出生后30~40 d(PND30~40)采用慢性不可预知性温和应激方法构建应激模型。根据窝别和性别将子代小鼠分为孕期免疫刺激+青春期应激组(P+S+组)、孕期免疫刺激组(P+S-组)、青春期应激组(P-S+组)和无刺激组(P-S-组),每组18只。其中P+S+组小鼠根据是否给予OLZ分为OLZ干预组(OLZ组)和非OLZ干预组(non-OLZ组),每组9只。分别于造模后和给予OLZ后采用声惊跳反射实验检测小鼠PPI功能状况。采用StatViewVersion 5.0软件进行数据分析,多因素方差分析法检验各因素的主效应、交互效应、简单效应。结果孕期免疫刺激及青春期应激主效应显著(F(1,330)=47.72,P<0.01),且二者存在显著交互作用(F(1,330)=14.80,P<0.01)。简单效应分析发现,P+S+组PPI%[(15.42±6.13)%]显著低于P+S-组[(27.33±4.58)%]、P-S+组[(31.17±3.97)%]、P-S-组[(47.14±12.28)%](均P<0.01)。不同性别间PPI值存在显著差异(F(1,396)=61.94,P<0.01),在雌雄性小鼠中,Prepulse+Pulse中不同强度Prepulse影响下的Pulse惊跳反应强度存在显著差异(F(1,198)=18.68、18.44,P<0.01),孕期免疫刺激有显著主效应(F(1,198)=32.18、12.58,P<0.01),与青春期应激存在显著交互作用(F(1,198)=34.54、11.39,P<0.01),按性别作简单效应分析发现,P+S+组雄性小鼠的Prepulse+Pulse的惊跳反应强度(0.47±0.12)显著高于P+S-组(0.36±0.11)、P-S+组(0.25±0.22)与P-S-组(0.31±0.19)(均P<0.01);P-S+组雌性小鼠的惊跳反应强度显著高于P+S+组和P+S-组、P-S-组(P<0.01)。OLZ能够逆转双重应激小鼠成年期PPI%的下降(F(1,165)=18.24,P<0.01)。OLZ能显著降低双重应激组雄性小鼠的PPI值(F(1,102)=21.81,P<0.01);OLZ能显著升高双�Objective To establish neurodevelopmental mice model of schizophrenia(SZ)with prepulse inhibition(PPI)deficits and investigate the effectiveness of olanzapine on PPI disruption.Methods On the 9th day of pregnancy of SPF grade C57BL/6 mice,female mice were injected with polyinosinic acid poly(I∶C)(6 mg/kg)through tail vein for immune stimulation.The stress model was constructed by chronic unpredictable mild stress 30-40 d after birth(PND30-40).The offspring mice were divided into pregnancy immune stimulation+adolescent stress group(P+S+group),pregnancy immune stimulation group(P+S-group),adolescent stress group(P-S+group)and non stimulation group(P-S-group),with 18 mice in each group.The mice in P+S+group were divided into OLZ intervention group(OLZ group)and non-OLZ intervention group(non-OLZ group),with 9 mice in each group.The PPI function of mice was detected by acoustic startle reflex test after modeling and OLZ intervention.Adopt StatView Version 5.0 software for data analysis,and multi factors analysis of variance was used to test the main effect,interactive effect and simple effect of each factor.Results The main effects of maternal Poly(I:C)immune activation and pubertal chronic unpredictable stress were significant(F(1,330)=47.72,P<0.01),and there was a significant interaction between the two factors(F(1,330)=14.80,P<0.01),simple effect analysis showed that average percent prepulse inhibition(PPI%)in P+S+group((15.42±6.13)%)was significantly decreased compared with groups of P+S-((27.33±4.58)%),P-S+((31.17±3.97)%)and P-S-((47.14±12.28)%)(all P<0.01).There was significant gender difference in Prepulse inhibition(PPI)score(F(1,396)=61.94,P<0.01),in male and female mice,average startle reactivity of Pulse under Prepulse+Pulse influence of distinct intensities was significantly different(F(1,198)=18.68,18.44,P<0.01),and the maternal Poly(I∶C)immune activation had a significant main effect(F(1,198)=32.18,12.58,P<0.01)and interaction with pubertal chronic unpredictable stress(F(1,198)=34.54,11.39,P<0.0

关 键 词：前脉冲抑制 精神分裂症 神经发育 聚肌苷酸-聚胞苷酸 动物模型 

分 类 号：R749.3[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]