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目的 利用孕期束缚应激诱导产后抑郁(PPD)大鼠模型，探索产后抑郁对子宫组织形态学特点、氧化应激指标、炎性因子及雌激素受体α(ERα)等的影响。方法 选择2～3月龄雌、雄性SD大鼠合笼，怀孕雌鼠随机分为对照组和PPD组，每组各6只。PPD组通过孕期束缚应激诱导构建PPD模型。两组大鼠在产后4～6 d,通过糖水偏好和强迫游泳实验检测抑郁样行为，采集血液检测血浆雌激素(E2)水平，通过HE染色观察子宫内膜形态，采用ELISA法检测子宫组织氧化应激指标[超氧化物歧化酶(SOD)、丙二醛(MDA)]及炎性因子白介素-1β(IL-1β)水平，实时荧光定量PCR法检测IL-1β及ERα mRNA表达水平，蛋白免疫印迹方法(Western blotting)检测ERα蛋白表达水平。结果 与对照组比较，PPD组大鼠糖水消耗率显著降低、强迫游泳不动时间显著延长(P均<0.01)。与对照组比较，PPD组大鼠血浆E2水平显著降低(P<0.01),子宫指数显著降低(P<0.01),内膜萎缩变薄，细胞缩小，间质部分纤维组织增生。与对照组比较，PPD组子宫组织中MDA含量显著增加、SOD活性显著降低(P均<0.01),炎性因子IL-1β表达量显著增加(P<0.05),ERα mRNA及蛋白表达水平均显著升高(P<0.01)。结论 孕期束缚应激可成功建立PPD大鼠模型；PPD可导致大鼠子宫发生相应的病理改变，如形态学变化、氧化应激水平及炎性因子、ERα表达增加等；但这些变化的具体机制尚需进一步探讨。
Abstract：Objective:To explore the effects of postpartum depression on uterine morphology, oxidative stress indicators, inflammatory factors, and estrogen receptor α(ERα) expression in a rat model of postpartum depression(PPD) induced by prenatal restraint stress.Methods:Female and male SD rats aged 2-3 months were selected for the study, and the pregnant female rats were randomly divided into control group and PPD group, with 6 rats in each group. PPD model rats in PPD group were constructed by inducing restraint stress during pregnancy. Two groups of rats were evaluated for depression-like behaviors through sugar water preference and forced swimming test at 4-6 days postpartum. Blood was collected to detect plasma estrogen(E2) levels, while biopsied uterine tissues were examined for endometrial morphology observed with HE staining. The oxidative stress indicators [superoxide dismutase(SOD),malondialdehyde(MDA)] and inflammatory factor interleukin-1β(IL-1β) were detected by ELISA. Real-time fluorescence quantitative PCR was employed to detect the expression of IL-1β mRNA and ERα mRNA,and ERα protein expression was detected by western blotting. Results:Compared with the control group, the PPD group showed a significant lower sugar water preference and a significant longer immobility duration in forced swimming(P<0.01). The plasma E2 levels and the uterine index in the PPD group were significantly lower than those in the control group(P<0.01),and the uterine morphology of PPD rats was characterized by endometrial atrophy and thinning, cell shrinkage, and proliferation of fibrous tissue in the stroma. Compared with the control group, PPD group showed a significant increase in MDA content(P<0.01),IL-1β expression(P<0.05) and both mRNA and protein expressions of ERα(P<0.01),while a significant reduced SOD activity(P<0.01) in the uterine tissues. Conclusions:Restraint stress during pregnancy can successfully establish PPD rats model. PPD can cause corresponding pathological changes in the uterus of rats, such as morphological changes, disorders of oxidative stress, increased levels of inflammatory factor and ERα expression. The specific mechanism of these changes is worth further exploration.
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基本信息:
中图分类号:R714.7;R-332
引用信息:
[1]李晓晓,吴文星,白云飞,等.产后抑郁大鼠子宫组织中氧化应激指标、炎性因子及雌激素受体表达分析[J].生殖医学杂志,2023,32(11):1710-1717.
基金信息:
国家自然科学基金面上项目(82071514,82271551,82174116); 北京市教委一般项目(KM202110025029)
2023-11-15
2023-11-15