早期干预对宫内感染致脑损伤仔鼠脑S-100蛋白及神经行为学的影响

Effects of Early Intervention on Expression of S-100 Protein and Neurobehavioral Change in Offspring Rats with Brain Injury Induced by Intrauterine Infection

目的研究早期干预对宫内感染致脑损伤仔鼠脑组织S-100蛋白表达和神经行为学的影响。方法孕第18天的Wistar大鼠连续2d腹腔注射脂多糖(LPS),制备宫内感染模型,9g·L-1盐水组给予同剂量9g·L-1盐水。随机选取9g·L-1盐水组仔鼠30只(对照组)和LPS组仔鼠50只。LPS组仔鼠随机分为干预组(n=20)和非干预组(n=30)。出生第1天非干预组和对照组各取10只大鼠,断头处死,取其脑组织,应用免疫组织化学方法测定其S-100蛋白水平,并在出生第25天对3组大鼠S-100蛋白水平行免疫组织化学检测和神经行为学检测。结果LPS组母鼠胎盘病理检测见胎盘内血管充血、水肿,并见大量中性粒细胞浸润,9g·L-1盐水组母鼠胎盘病理检测未见明显炎症反应;非干预组1日龄仔鼠脑组织各部位S-100蛋白阳性染色与对照组仔鼠比较,均有明显增加(Pa<0.01);25日龄仔鼠中,非干预组S-100蛋白表达最强,对照组最弱,干预组介于两者之间,各组间两两比较差异有统计学意义(Pa<0.01);非干预组仔鼠在悬吊试验、姿势反射、肌张力、不自主运动、旷场试验中的得分明显低于干预组和对照组,干预组明显高于非干预组(Pa<0.05),但低于对照组(Pa<0.05);非干预组斜坡试验中所用时间最长,干预组所用时间明显短于非干预组(P<0.05),但所用时间仍长于对照组(P<0.05)。结论宫内感染可诱发新生大鼠脑损伤,S-100蛋白表达明显增多,早期干预可通过减少S-100蛋白表达,改善脑损伤仔鼠运动和行为异常。

Objective To research the effects of early intervention on the expression of S-100 protein and neurobehavioral change in offspring rats with brain injury induced by intrauterine infection.Methods Wistar rats in intrauterine infection group received lipopolysaccharide（LPS） intraperitoneal injection on the 18th day after getting pregnant,and the rats in normal saline group received the same dosage of normal saline.The placenta of rats in two groups were taken to detect the pathology after litter size.Thirty offspring rats were taken from the normal saline group randomly as control group,and 50 offspring rats selected from intrauterine infection group were divided into intervention group（n=20） and non-intervention group（n=30）.On the every day after birth,10 rats were taken from non-intervention group and control group respectively,and their brains were taken to detect the expression of S-100 protein.Twenty-five days after birth,the neurobehavioral changes in these groups were observed,and the expressions of S-100 protein in these groups were detected by immunohistochemistry.Results The placenta of rats in LPS group showed vascular engorgement,dropsy,and neutrophilic granulocyte soakage.Compared with control group,the expression of S-100 protein in non-intervention group was markedly increased（Pa0.01） in 1 day-old rats.The most strong expression of S-100 protein appeared in non-intervention group,and the most weak expression appeared in the control group,while the expression of S-100 protein in intervention group was between them,in 25 day-old rats,the differences between the 2 groups were significant（Pa0.01）.In suspension experiment,postural reflex,muscle tension test,involuntary movement test and open field test,the scores of non-intervention group were lowest,the scores of these test in intervention group were higher than non-intervention group（Pa0.05） but still lower than those in control group（Pa0.05）.Rats in non-intervention group spend more time than that in intervention group and control group,after intervention,animals in intervention group did better than those in non-intervention group（Pa〈0.05）,but still spend more time than rats in control group（Pa〈0.05）.Conclusions Intrauterine infection could induce brain damage of offspring rats and increase the expression of S-100 protein.Early intervention could decrease the expression of S-100 protein and improve the rehabilitation of motion abnormality and dystropy of rats induced by brain damage.