山西医科大学学报2025，Vol.56Issue(2)：158-164,7.DOI:10.13753/j.issn.1007-6611.2025.02.007
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
摘要
Abstract
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-1β and TNF-α were 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-1β and TNF-α in the hippocampus of offsprings were higher in stress group than in control group(P<0.01).Western blot results indicated that compared with control group,the expression of Iba1 protein was increased(P<0.05),while the protein expressions of Nrf 2 and HO-1 were decreased(P<0.01).Immunofluorescence findings were consistent with the results of Western blot.Conclusion Stress during pregnancy in rats leads to the antioxidant imbalance in adult offsprings,which affects the cognitive function of adult offsprings by activating microglia via the Nrf2/HO-1 pathway.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Key words
prenatal stress/microglia/Nrf2/behavior testing/cognitive dysfunction/superoxide dismutase分类
医药卫生引用本文复制引用
田晓寒,吕梦姣,周晓丹,王梦慈,袁孙强,廖礼彬,白生宾..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[J].山西医科大学学报,2025,56(2):158-164,7.基金项目
国家自然科学基金资助项目(82160356) （82160356）
