孕期应激子代脑内抗氧化失衡对子代认知功能的影响及作用机制  

Effects and molecular mechanism of antioxidant imbalance on cognitive function and microglia in offsprings of rats with prenatal stress

作　　者：田晓寒 吕梦姣 周晓丹 王梦慈 袁孙强 廖礼彬[1] 白生宾[1] TIAN Xiaohan;LU Mengjiao;ZHOU Xiaodan;WANG Mengci;YUAN Sunqiang;LIAO Libin;BAI Shengbin(Department of His-tology,School of Basic Medical Sciences,Xinjiang Medical University,Xinjiang Key Laboratory of Endemic Diseases,Urumqi 830011,China)

机构地区：[1]新疆医科大学基础医学院组胚教研室,新疆地方病分子生物学重点实验室,乌鲁木齐830011

出　　处：《山西医科大学学报》2025年第2期158-164,共7页Journal of Shanxi Medical University

基　　金：国家自然科学基金资助项目(82160356)。

摘　　要：目的 探讨大鼠孕期应激子代脑内抗氧化失衡对子代认知功能及小胶质细胞的影响及分子机制。方法 12只SD孕鼠被随机分为应激组和对照组,每组6只,应激组在孕15~20 d给予限制性应激,对照组不予应激处理。通过旷场、高架十字迷宫及Y迷宫3种行为学试验检测8~9周龄成年子代认知功能,微量法检测8~9周龄成年子代外周血中超氧化物歧化酶(superoxide dismutase,SOD)活性及丙二醛(MDA)水平,免疫组化法检测子代海马CA1区小胶质细胞变化及Iba1表达,qRT-PCR检测子代海马IL-1β、TNF-α的mRNA相对含量,免疫荧光法检测子代海马CA1区Nrf2、HO-1、Iba1表达,Western blot检测子代海马Nrf2、HO-1、Iba1蛋白表达。结果 旷场试验结果显示,与对照组相比,应激组子代5 min内运动总路程未见明显差异,中央区路程明显减少(P<0.05);高架十字迷宫结果显示,与对照组相比,应激组子代在开放臂停留时间和进入开放臂次数百分比明显减少(P<0.05);Y迷宫结果显示,与对照组相比,应激组子代自主交替率明显减少(P<0.05)。与对照组相比,应激组外周血中SOD活性升高(P<0.01)、MDA水平降低(P<0.05)。免疫组化结果显示,与对照组相比,应激组子代海马CA1区小胶质细胞形态改变,激活数量增加(P<0.05)。qRT-PCR结果显示,与对照组相比,应激组子代海马中IL-1β、TNF-α的mRNA相对含量升高(P<0.01)。Western blot结果显示,与对照组相比,应激组子代海马区Iba1蛋白表达升高(P<0.05),Nrf2及HO-1蛋白表达下降(均P<0.01);免疫荧光与Western blot结果一致。结论 大鼠孕期应激导致成年子代脑内抗氧化失衡,并通过影响Nrf2/HO-1通路激活小胶质细胞,从而影响成年子代认知功能。Objective To explore the effects of antioxidant imbalance on cognitive function and microglia in offsprings of rats with prenatal stress.Methods Twelve pregnant SD rats were randomly divided into control group and stress group,with 6 rats in each group.The rats in stress group underwent restricted stress at prenatal days 15-20,and the rats in control group were given no stress.The cognitive function of adult offsprings aged 8-9 weeks was detected by open field test,elevated plus maze test and Y maze test.Su-peroxide dismutase(SOD)and malondialdehyde(MDA)levels were detected in peripheral blood of 8-9-week-old adult offsprings by micromethod.Iba1 expression in the CA1 region of the offspring hippocampus was detected by immunohistochemistry.The relative mRNA levels of IL-1βand TNF-αwere detected by qRT-PCR.The expressions of Nrf2,HO-1,and Iba1 in the CA1 region of offspring hippocampus were detected by immunofluorescence.The protein expressions of Nrf 2,HO-1,and Iba1 in the offspring hippocampus were determined by Western blot.Results The open field test indicated that,compared with control group,there was no significant difference in the total distance within 5 min in stress group,while the distance in the central area was significantly reduced(P<0.05).The elevated plus maze results demonstrated that the offsprings spent less time in the open arms and had a lower percentage of entries into the open arms in stress group than in control group(P<0.05).Y-maze results showed that the spontaneous alternation rate of the offspring in stress group was significantly lower than that in control group(P<0.05).Compared with control group,SOD activity was in-creased in stress group(P<0.01),while MDA level was decreased(P<0.05).Immunohistochemical results revealed that the number of activated microglia in the CA1 region of the hippocampus in the offspring in stress group was higher than in control group(P<0.05).The qRT-PCR results demonstrated that the mRNA levels of IL-1βand TNF-αin the hippocampus of offsprings were higher

关 键 词：孕期应激 小胶质细胞 NRF2 行为学检测 认知功能障碍 超氧化物歧化酶 

分 类 号：R338[医药卫生—人体生理学]