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浙江大学学报（医学版）
浙江大学学报（医学版）  2019, Vol. 48 Issue (1): 58-64    DOI: 10.3785/j.issn.1008-9292.2019.02.10
原著     
宫内感染对新生大鼠早期生长及神经行为发育的影响
沈盈1(),孙逸1,顾伟忠2,俞惠民1,袁天明1()
1. 浙江大学医学院附属儿童医院新生儿科， 浙江 杭州 310052
2. 浙江大学医学院附属儿童医院病理科， 浙江 杭州 310052
Intrauterine infection affects early growth and neurobehavioral development in neonatal rats
SHEN Ying1(),SUN Yi1,GU Weizhong2,YU Huimin1,YUAN Tianming1()
1.Departments of Neonatology, the Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China
2.Departments of Pathology, the Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China
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摘要： 目的

探讨宫内感染对新生大鼠出生后早期生长发育和神经行为发育的影响。

 方法

通过将大肠埃希菌注入孕15 d的SD大鼠的子宫颈内建立宫内感染大鼠模型，并观察宫内感染对孕鼠分娩的影响。HE染色法观察新生大鼠脑白质组织病理学变化；免疫组织化学染色和蛋白质印迹法检测新生大鼠脑白质组织胶质细胞原纤维酸性蛋白（GFAP）、2′，3′-环核苷酸磷酸二酯酶（CNPase）、神经丝（NF）表达。随机监测新生大鼠早期生长发育和神经行为功能。

 结果

孕鼠宫内感染后，子宫和胎盘组织白细胞计数升高，提示建模成功，但宫内感染对分娩无显著影响。新生大鼠7日龄时脑白质部位结构稀疏呈筛网状改变，GFAP表达增加（P＜0.01），而CNPase和NF表达减少（P＜0.05或P＜0.01）。与对照组新生大鼠比较，感染组新生大鼠出生体质量轻、体质量增长缓慢（P＜0.05或P＜0.01）；耳廓分离、睁眼、平面翻正、负趋地性、听觉惊恐和游泳试验等完成日龄延长（P＜0.05或P＜0.01）。

 结论

宫内感染可导致新生大鼠脑白质损伤，并引起新生大鼠早期生长发育及神经行为发育延迟。
关键词： 妊娠并发症，感染性;  大肠杆菌;  神经系统/生长和发育;  疾病模型，动物    
Abstract: Objective

To explore the effects of intrauterine infection on early growth and neurobehavioral development in neonatal rats.

 Methods

Escherichia coli (E. coli) was inoculated into uterine cervix of pregnant rats with gestation of 15 d to establish the intrauterine infection model, and the effect on the delivery of pregnant rats was observed. The neonatal rat brain tissue was stained with Hematoxylin-Eosin and the cerebral white matter damage was assessed. Immunohistochemical staining and Western blot analysis were performed to evaluate the expression of glial fibrillary acidic protein (GFAP), 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and neurofilament (NF) in pup brains. Birth weight and early growth development indices were monitored， and neurobehavioral tests were performed to access the change of neurobehavioral development in neonatal rats.

 Results

The white blood cell count increased significantly in the uterus and placenta of the pregnant rats after intrauterine E. coli infection and no significant impact was observed on the delivery of pregnant rats. Weak staining and focal rarefaction of cerebral white matter from rats at P7 in intrauterine infection group were observed. The expression of GFAP markedly increased (P＜0.05) in infection group, while the level of CNPase and NF in pup brains at P7 significantly decreased (P＜0.05 or P＜0.01). Compared with control group, the neonatal rats in infection group had lower birth weight and slower weight gain during the suckling period (P＜0.05 or P＜0.01), and the completion times of ear opening, eye opening, surface righting, negative geotaxis, acoustic startle and swimming test in infection group were significantly delayed (P＜0.05 or P＜0.01). Conclussion: Intrauterine infection in pregnant rats can induce cerebral white matter damage and retardation of early growth and neurobehavioral development in neonatal rats.
Key words: Pregnancy complications, infectious    Escherichia coli    Nervous system/ growth & development    Disease models, animal
收稿日期: 2018-11-20 出版日期: 2019-05-10
:  R722.19  
基金资助: 国家自然科学基金(81571466，81000266)
通讯作者: 袁天明     E-mail: sherrill@zju.edu.cn;yuantianming@zju.edu.cn
作者简介: 沈　盈（1981—），女，博士，主治医师，主要从事新生儿脑损伤研究；E-mail： sherrill@zju.edu.cn； https://orcid.org/0000-0002-9172-0972|袁天明（1973—），男，博士，主任医师，硕士生导师，主要从事新生儿感染性疾病及新生儿脑损伤研究；E-mail： yuantianming@zju.edu.cn； https://orcid.org/0000-0003-2593-606X
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沈盈
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引用本文:

沈盈,孙逸,顾伟忠,俞惠民,袁天明. 宫内感染对新生大鼠早期生长及神经行为发育的影响[J]. 浙江大学学报（医学版）, 2019, 48(1): 58-64.

SHEN Ying,SUN Yi,GU Weizhong,YU Huimin,YUAN Tianming. Intrauterine infection affects early growth and neurobehavioral development in neonatal rats. J Zhejiang Univ (Med Sci), 2019, 48(1): 58-64.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2019.02.10    或    http://www.zjujournals.com/med/CN/Y2019/V48/I1/58

图1  HE染色观察宫内感染孕鼠子宫和胎盘的组织病理学变化
图2  HE染色观察孕鼠宫内感染后分娩的新生大鼠7日龄时脑白质组织病理学变化
图3  免疫组织化学染色观察孕鼠宫内感染后分娩的新生大鼠7日龄时脑白质中GFAP、CNPase、NF蛋白表达
图4  孕鼠宫内感染后分娩的新生大鼠7日龄时脑白质中GFAP、CNPase和NF蛋白表达电泳图
图5  孕鼠宫内感染后分娩的新生大鼠早期生长发育相关指标变化
图6  孕鼠宫内感染后分娩的新生大鼠神经行为功能指标变化
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