目的 运用功能核磁共振成像(functional magnetic resonance imaging,fMRI)研究愈癫汤对精神分裂症(schizophrenia,SZ)模型大鼠脑功能连接(functional connectivity,FC)的影响.方法 健康SPF级SD大鼠孕17 d时,单次腹腔注射甲基氧化偶氮甲醇(methylazoxymethanol,MAM)(25 mg/kg),以孕期母鼠单胺类神经递质异常建立仔鼠神经发育异常模型,选取4周龄雄性仔鼠作为SZ模型大鼠.30只SZ模型大鼠按照体质量相匹配方法分为模型组、实验组、阳性对照组,每组10只,另取健康母鼠所生的10只雄性仔鼠作为空白对照组.各组大鼠6周龄时,实验组和阳性对照组大鼠分别灌胃愈癫汤(1.54 g/kg)和利培酮(0.24mg/kg),空白对照组和阳性对照组大鼠均灌胃蒸馏水(6.7mL/kg),1次/d,连续灌胃14 d.使用3.0T核磁共振扫描仪进行脑扫描,获取所有样本的fMRI数据.将双侧海马、双侧前额叶、双侧纹状体作为感兴趣区(region of interest,R0I)进行统计分析,采用双样本t检验两两比较ROI之间的FC以及全脑的FC.结果 (1)模型组大鼠在左侧小脑颗粒细胞层(SIGMA:x=-2,y=-107,z=48)相比空白对照组全脑FC增强(簇大小=43,簇水平PFWE＜0.05);实验组在左侧小脑分子层(SIGMA:x=-5,y=-152,z=36)相比模型组全脑FC增强(簇大小=48,P＜0.05,簇水平FWE校正).(2)以双侧海马作为ROI,阳性对照组在上丘深层(SIGMA:x=13,y=-77,z=27)相比模型组FC增强(簇大小=88,P＜0.05,簇水平FWE校正);空白对照组在右侧颗粒状岛叶皮质(SIGMA:x=43,y=19,z=9)相比模型组FC减弱(簇大小=125,P＜0.05,簇水平FWE校正);以双侧前额叶作为ROI,实验组在左侧小脑分子层(SIGMA:x=-14,y=-128,z=48)相比空白对照组FC减弱(簇大小=68,P＜0.05,簇水平FWE校正).结论 SZ存在全脑功能连接异常,特别是海马区的功能性增强,愈癫汤可以抑制其中前额叶的活动性.
Effect of Yudian decoction on brain functional connectivity in schizophrenic model rats:an functional magnetic resonance imaging study
Objective To investigate alterations in brain functional connectivity(FC)in schizo-phrenia(SZ)model rats treated with Yudian decoction by using functional magnetic resonance imaging(fMRI).Methods At 17th day of gestation in healthy SPF grade SD rats,a single intraperitoneal injection of methylazoxymethanol(MAM)(25 mg/kg)was used to induce abnormalities in monoamine neurotransmit-ters in pregnant female rats,thereby to establish a model of neural development abnormalities in the off-spring.Four weeks old male offspring were selected as SZ model rats.Thirty SZ model rats were divided into model group,experimental group,and positive control group according to the body mass matching method,with 10 rats in each group.Additionally,10 male offspring born to healthy female rats were selected as the blank control group.At 6 weeks of age,the rats in experimental group and positive control group were admin-istered with Yudian decoction(1.54 g/kg)and risperidone(0.24 mg/kg)by gavage,respectively.The rats in blank control group and positive control group were administered with distilled water(6.7 mL/kg)by ga-vage.All the above interventions were conducted once a day for 14 consecutive days.The fMRI data were ac-quired from all samples using a 3.0 T MRI scanner.The bilateral hippocampus,bilateral prefrontal cortex,and bilateral striatum were designated as region of interest(ROI).FC comparisons between each pair of ROIs and whole-brain FC were conducted using two-sample t-test.Results(1)Compared to the control group,the model group demonstrated enhanced whole-brain FC at the left cerebellar granular cell level(SIGMA:x=-2,y=-107,z=48)(cluster size=43,P＜0.05,FWE adjusted under cluster-level).The ex-perimental group exhibited increased whole-brain FC at the left cerebellar molecular layer(SIGMA:x=-5,y=-152,z=36)compared to the model group(cluster size=48,P＜0.05,FWE adjusted under cluster-lev-el).(2)Using the bilateral hippocampus as ROI,the positive control group exhibited enhanced FC at the deep layer of the superior colliculus(SIGMA:x=13,y=-77,z=27)compared to the model group(cluster size=88,P＜0.05,FWE adjusted under cluster-level).The blank control group displayed decreased FC at the right granular insular cortex(SIGMA:x=43,y=19,z=9)compared to the model group(cluster size=125,P＜0.05,FWE adjusted under cluster-level).Utilizing the bilateral prefrontal cortex as ROI,the experi-mental group showed reduced FC at the left cerebellar molecular layer(SIGMA:x=-14,y=-128,z=48)compared to the blank control group(cluster size=68,P＜0.05 FWE adjusted under cluster-level).Conclusion Schizophrenia is associated with abnormal whole-brain functional connectivity,notably charac-terized by enhanced functional connectivity in the hippocampal region.Yudian decoction demonstrates the ca-pability to inhibit activity in the prefrontal cortex.
Functional magnetic resonance imaging(fMRI)Yudian decoctionSchizophreniaFunctional connectivityRat
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