孕期慢性应激对不同性别仔鼠情绪损伤的影响

Effects of chronic stress during pregnancy on sex-specific offspring emotional damage

  • 摘要:
    背景  研究表明孕期应激会影响胎儿及子代的生长发育,这种影响存在性别差异,但研究结果有较大争议,且对孕期应激致不同性别仔鼠情绪损伤研究甚少。
    目的  观察孕期慢性应激对不同性别仔鼠情绪损伤影响的差异。
    方法  将32只SD雌鼠随机分为模型组和对照组(每组16只);24只雄鼠分为模型交配组(16只)和对照交配组(8只)。模型组采用单笼饲养方式和慢性不可预知温和应激(CUMS)进行28 d的随机应激,包括:热水浴5 min、冰水浴5 min、夹尾2 min、拥挤24 h、潮湿垫料24 h、摇晃鼠笼30 min,狭小空间束缚2 h。每日进行一种应激,一周内相同的应激刺激方式不重复出现。在应激前1天和应激第1、7、14、21、28天对两组母鼠进行内眦静脉采血,离心分离血浆,用131I放射性免疫法测定血浆皮质酮浓度。在仔鼠出生后第21天(PND21),每组各随机抽取16只(雌雄各半)为研究对象。在PND28、PND42测定仔鼠的血浆皮质酮浓度,在PND42测定仔鼠情绪损伤情况。
    结果  在应激第14、21、28天,模型组母鼠血浆皮质酮浓度(394.02±97.40)、(444.12±90.43)、(463.71±107.75)μg·L−1高于对照组母鼠 (285.63±81.64)、(341.78±48.39)、(320.42±84.76)μg·L−1(均P<0.05)。雌性模型仔鼠组在PND28和PND42的血浆皮质酮浓度(543.30±90.21)、(530.76±83.10)μg·L−1均高于同性别对照仔鼠组(397.77±>64.27)、(325.78±61.03)μg·L−1(均P<0.05)。雌性模型仔鼠组蔗糖偏好实验的液体总消耗(10.74±1.28)mL、糖水消耗(5.50±1.30)mL和1%蔗糖偏好百分比(20.36±3.41)%低于同性别对照仔鼠组(13.74±2.06)mL、(8.56±2.04)mL和(62.11±8.05)%(均P<0.05)。雄性模型仔鼠组旷场实验的水平得分、垂直得分以及清洁次数均低于雄性对照仔鼠组(均P<0.05)。雌性、雄性模型仔鼠组悬尾实验的静止持续时间(126.95±39.88)、(70.24±28.98)s均长于同性别的对照仔鼠(54.30±24.99)、(38.63±18.91)s (均P<0.05),且雌性模型仔鼠组静止持续时间更长(t=3.253,P=0.006)。在强迫游泳实验的不动持续时间上,雌性模型仔鼠(7.97±6.66)s长于同性别的对照仔鼠组(1.85±2.12)s(t=2.478,P=0.037)。PND42时,雌性仔鼠血浆皮质酮与液体总消耗、糖水消耗、1%蔗糖偏好百分比呈负相关(r=−0.621,r=−0.728,r=−0.699;P<0.05),与静止持续时间和不动持续时间呈正相关(r=0.571,r=0.712;P<0.05),而雄性仔鼠血浆皮质酮与PND42时情绪各项指标未见相关性(均P>0.05)。
    结论  孕期慢性应激致仔鼠的情绪发生损伤,雌性仔鼠表现出抑郁样情绪。

     

    Abstract:
    Background  Studies have shown that stress during pregnancy can affect the growth and development of fetuses and offspring, and this effect has sex differences, but the results are controversial, and there are few studies on the emotional damage of offspring of different sexes caused by stress during pregnancy.
    Objective  This experiment is designed to observe the effect of chronic stress during pregnancy on emotional damage of offspring of different sexes.
    Methods  Thirty-two SD female rats were randomly divided into a model group and a control group (16 rats in each group), 24 male rats were divided into a model mating group (n=16) and a control mating group (n=8). Each rat of the model group was reared in a single cage and received chronic unpredictable mild stress (CUMS) for 28 d, including hot water swimming for 5 min, cold water swimming for 5 min, tail pinching for 2 min, crowding for 24 h, moist bedding for 24 h, cage shaking for 30 min, and space restriction for 2 h. One stressor was administered daily and the same stressor did not repeat within 7 d. Blood was collected from the endocanthal vein of the two groups of female rats 1 d before and 1, 7, 14, 21, and 28 d after stress, the plasma was separated by centrifugation, and 131I radioimmunoassay was used to measure plasma corticosterone concentration. On postnatal day 21 (PND21), 16 offspring rats (half male and half male) were randomly selected from each group, their plasma corticosterone concentration was measured on PND28 and PND42, and their emotional damage was measured on PND42.
    Results  The plasma corticosterone levels of dams in the model group on the 14th, 21th, and 28th days of stress (394.02±97.40), (444.12±90.43), and (463.71±107.75) μg·L−1 were higher than those in the control group (285.63±81.64), (341.78±48.39), and (320.42±84.76) μg·L−1 (all P< 0.05). On PND28 and PND42, the plasma corticosterone levels in the female model offspring group (543.30±90.21) and (530.76±83.10) μg·L−1 were higher than those in the female control offspring group (397.77±64.27) and (325.78±61.03) μg·L−1 (both P<0.05). In the sugar water preference test, the total fluid consumption (10.74±1.28) mL, sugar water consumption (5.50±1.30) mL, and 1% sucrose preference percentage (20.36±3.41) % in the female model offspring group were lower than those in the female control offspring group (13.74±2.06) mL, (8.56±2.04) mL, and (62.11±8.05) % (allP<0.05). In the open field test, the horizontal score, vertical score, and cleaning times of the male model offspring group were lower than those of the male control offspring group (allP<0.05). In the tail suspension test, the immobility time of the female and male model offspring groups (126.95±39.88) and (70.24±28.98) s was longer than the control offspring groups of the same sex (54.30±24.99) and (38.63±18.91) s (bothP<0.05), and the duration of immobility time in the female model offspring group was longer (t=3.253, P=0.006). In the forced swimming test, the immobility time of the female model offspring group (7.97±6.66) s was longer than that of the female control offspring group (1.85±2.12) s (t=2.478, P=0.037). On PND42, the plasma corticosterone level of female offspring was negatively correlated with total fluid consumption, sugar water consumption, and 1% sucrose preference percentage (r=−0.621, r=−0.728, r=−0.699; P<0.05), and positively correlated with immobility time in the tail suspension test and immobility time in the forced swimming test (r=0.571, r=0.712; P<0.05), However, there was no correlation between plasma corticosterone and emotional indicators on PND42 in male offspring (P>0.05).
    Conclusion  Chronic stress during pregnancy causes emotional damage to the offspring, and female offspring show depression-like behaviors.

     

/

返回文章
返回