母鼠妊娠前慢性不可预见性应激对子代大鼠大脑脑源性神经营养因子-酪氨酸激酶受体通路的影响

Effect of chronic and unpredictable pre-gestational stress on the brain-derived neurotrophic factor-tyrosine protein kinase B signal transduction pathway in the brain of the offspring rats

目的 探讨母鼠妊娠前慢性不可预见性应激（CUS）对2月龄子代大鼠血清皮质醇（COR）水平以及大脑海马脑源性神经营养因子（BDNF）和酪氨酸激酶受体（TrkB）表达的影响.方法 SD系雌性大鼠简单随机分为正常组和CUS模型组.采用11种刺激方法对CUS模型组母鼠进行21 d慢性不可预见性应激.2组母鼠分别于造模前后行开场试验及蔗糖消耗试验.用放射免疫法检测2月龄子代大鼠血清COR水平,并用免疫组织化学法检测其海马BDNF和TrkB的表达情况.结果 1.CUS模型组母鼠在应激后的开场试验的总路程、周边路程、中央路程和蔗糖消耗试验的蔗糖水消耗量明显少于应激前及正常对照组母鼠.2.子代大鼠血清COR水平分别为：正常雌性子代组（119.9±9.0） μg/L,CUS雌性子代组（128.9±7.3） μg/L,正常雄性子代组（105.4±10.4）μg/L,CUS雄性子代组（116.5 ±10.9）μg/L,2组同性别子代大鼠间的差异有统计学意义,但体质量和脑质量的差异均无统计学意义.3.子代大鼠海马BDNF表达的相对灰度值分别为：正常雌性子代组（42.4±6.9）,CUS雌性子代组（36.1±8.5）,正常雄性子代组（43.7 ±6.4）,CUS雄性子代组（39.6±8.4）,2组同性别子代大鼠间的差异有统计学意义.4.子代大鼠海马TrkB表达的相对灰度值分别为：正常雌性子代组（50.2±3.9）,CUS雌性子代组（47.1±2.9）,正常雄性子代组（50.5±5.4）,CUS雄性子代组（46.5±6.7）,2组同性别子代大鼠间的差异有统计学意义.结论 母鼠妊娠前CUS会使子代大鼠大脑海马BDNF及TtkB的表达减少,其机制可能与下丘脑-垂体-肾上腺轴调节功能失常有关.

Objective To investigate the effect of chronic and unpredictable pre-gestational stress on the serum cortisol level of the offspring,as well as the expressions of brain-derived neurotrophic factor （BDNF） and tyrosine protein kinase B （TrkB） in hippocampus when they were 2 month old.Methods Adult female SD rats were divided randomly into 2 groups：the control group and the chronic unpredictable stress （CUS） model group.All rats were tested in the open field test and sucrose intake test before and after CUS protocol.All offspring rats were sacrificed when 2-month old.Serum cortisol （COR） levels were determined by using a standard radioimmunoassay kit.The expressions of BDNF and TrkB in hippocampus were studied by immunoreactivity quantitative analysis.Results 1.After CUS procedure,CUS group showed decreasing activities in the open field test and decreasing sucrose consumption in sucrose intake test compared to the control group and before CUS procedure.2.The serum COR levels in the female offspring rats of CUS group （128.9 ± 7.3） μg/L were higher than those of the control group （119.9 ± 9.0） μg/L,as well as the male offspring of CUS group（116.5 ± 10.9） μg/L compared with the control group（105.4 ± 10.4） μg/L,but the body weight and brain weight between the offspring of 2 groups were not statistic significance.3.Immunoreactivity quantitative analysis showed that the gray values of BDNF in the female offspring of CUS group （36.1 ± 8.5） decreased compared with the control group（42.4 ± 6.9）,as well as the male offspring of CUS（39.6 ± 8.4）compared with the control group （43.7 ± 6.4）.4.The gray values of TrkB in the female offspring of CUS group （47.1 ± 2.9） decreased than the control group（50.2 ± 3.9）,as well as the male offspring of CUS （46.5 ± 6.7）compared with control group（50.5 ± 5.4）.Conclusion Pre-gestational stress reduced the expressions of BDNF and TrkB in hippocampus of the offspring which may relate to hypothalamic pituitary adrenal.