摘要
目的探究妊娠期糖尿病(GDM)对子代社交行为的影响。方法4周龄雌性SD大鼠,根据体重随机分为空白对照(CON)组和妊娠期糖尿病(GDM)组,各组孕鼠受孕后,GDM组采用高脂膳食(HFD)辅以小剂量链脲佐菌素(STZ,30 mg/kg·bw)注射的方法建立疾病模型。各组孕鼠自然分娩,子代分别在分娩后第21天(PND 21,断乳)、PND 56(性成熟期)、PND 98(成年期)三个时期开展旷场实验(OFT)、高架十字迷宫实验(EPM)、新物体识别实验(NOR)和三箱社交实验(3-CST)来评估大鼠的社交行为,并在各个时期测定子代海马组织中的关键蛋白表达情况,以及白细胞介素-1β(IL-1β)、IL-4、IL-6、IL-10等细胞因子浓度。结果与CON组相比:GDM雌性子代在PND 98的旷场实验自主活动得分显著降低(P<0.05);GDM雄性子代在PND 98的高架十字迷宫实验中,开放臂停留时间百分比显著降低(P<0.05)。新物体识别实验中GDM雌性子代在PND 21的新物体偏爱指数显著降低(P<0.05);三箱社交实验中,GDM雌性子代在PND 21和GDM雄性子代在PND 98的社交倾向指数显著降低(P<0.05);GDM雌雄子代在PND 98的社交新奇偏好指数也显著降低(P<0.05)。与CON组相比:GDM雌性子代在PND 21的p-ERK、p-CREB表达显著上调,BDNF表达显著下调(P<0.05),在PND 56的p-TrkB表达显著下调(P<0.05),在PND 98的p-ERK、BDNF表达显著下调(P<0.05);GDM雄性子代在PND 21的p-ERK表达显著上调(P<0.05),p-CREB表达显著下调(P<0.05),在PND 56的p-TrkB表达显著下调(P<0.05),在PND 98的p-ERK表达显著下调(P<0.05)。与CON组相比:GDM雌性子代在PND 21的海马IL-1β、IL-4、IL-6浓度显著下降(P<0.05),在PND 56的海马IL-6浓度显著升高(P<0.05),在PND 98的海马IL-4浓度显著降低,IL-10浓度显著升高(P<0.05);GDM雄性子代在PND 21的海马IL-4、IL-6、IL-10浓度显著下降(P<0.05),在PND 56的海马IL-1β、IL-10浓度显著升高(P<0.05),在PND 98的海马IL-4浓度显著降低,IL-6浓度显著升高(P<0.05)。结论GDM子代的社交行为在生命早期无明显改变,在成年期出现较为明显的社交障碍,且该种作用不具有明显的性别特异性。
Objective To investigate the impact of gestational diabetes mellitus(GDM)on social behavior in rat offspring.Methods Female Sprague-Dawley rats at 4 weeks of age were randomly divided into a control group(CON)and a gestational diabetes group(GDM)based on body weight.The GDM group was induced with a high-fat diet(HFD)and a low-dose injection of streptozotocin(STZ,30 mg/kg·bw)to establish the disease model.After natural delivery,the offspring were subjected to open field test(OFT),elevated plus maze test(EPM),novel object recognition test(NOR),and three-chamber social test(3-CST)at three time points:postnatal day 21(PND 21,weaning),PND 56(sexual maturation),and PND 98(adulthood)to evaluate their social behavior.The concentrations of interleukin-1β(IL-1β),IL-4,IL-6 and IL-10 in offspring hippocampal tissues were measured at each time point.Results Compared to the CON group,female offspring in the GDM group showed a significant decrease in spontaneous activity scores in the OFT at PND 98(P<0.05).Male offspring in the GDM group exhibited a significant decrease in the percentage of time spent in the open arms in the EPM at PND 98(P<0.05).In the NOR,female offspring in the GDM group showed a significant decrease in the novelty preference index at PND 21(P<0.05).In the 3-CST,female offspring in the GDM group had a significant decrease in the social preference index at PND 21,and male offspring in the GDM group had a significant decrease in the social preference index at PND 98(P<0.05).The social novelty preference index was also significantly decreased in both male and female offspring in the GDM group at PND 98(P<0.05).In the hippocampus,compared to the CON group,among female offspring in the GDM group,the relative expression of p-ERK and p-CREB increased significantly while the relative expression of BDNF protein decreased significantly at PND 21(P<0.05),and the relative expression of p-TrkB decreased significantly at PND 56(P<0.05),and the relative expression of p-ERK and BDNF decreased significantly at PND 98(P<0.05).Compared to the CON group,among male offspring in the GDM group,the relative expression of p-ERK increased significantly while the relative expression of p-CREB decreased significantly at PND 21(P<0.05),the relative expression of p-TrkB decreased significantly at PND 56(P<0.05),and the relative expression of p-ERK decreased significantly at PND 98(P<0.05).Compared to the CON group,female offspring in the GDM group showed a significant decrease on the concentration of hippocampal IL-1β,IL-4 and IL-6 at PND 21(P<0.05),and their hippocampal IL-6 concentration had significantly increased at PND 56(P<0.05),and the IL-4 concentration decreased significantly,while the IL-10 concentration increased significantly at PND 98(P<0.05).Male offspring in the GDM group showed a significant decrease on the concentration of hippocampal IL-4,IL-6 and IL-10 at PND 21(P<0.05),and a significant increase on concentration of hippocampal IL-1βand IL-10 at PND 56(P<0.05),and their IL-4 concentration decreased significantly,while the IL-6 concentration increased significantly at PND 98(P<0.05).Conclusion The social behavior of GDM offspring does not show significant changes in early life but exhibits noticeable social impairments in adulthood,without significant gender specificity.
作者
史涵旭
叶湾韵
周雅琳
文彰
彭译乐
许雅君
SHI Hanxu;YE Wanyun;ZHOU Yalin;WEN Zhang;PENG Yile;XU Yajun(Department of Nutrition and Food Hygiene,Peking University,Beijing,100191;Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety,Beijing,100191)
出处
《中国生育健康杂志》
2025年第5期430-437,共8页
Chinese Journal of Reproductive Health
基金
国家自然科学基金(82173500)。
关键词
妊娠期糖尿病
社交行为
细胞因子
gestational diabetes mellitus
social behavior
cytokine
