妊娠期和哺乳期持续氟铝联合暴露对仔鼠海马环磷酸腺苷-蛋白激酶A-环磷酸腺苷反应元件结合蛋白信号通路的影响

发布时间：2018-12-25 19:46

【摘要】：目的探讨妊娠期和哺乳期持续染毒对子二代大鼠海马组织内环磷酸腺苷(cAMP)-蛋白激酶A(PKA)-环磷酸腺苷反应元件结合蛋白(CREB)信号通路的影响。方法将36只健康成年清洁级SD孕鼠随机分为9组,分别为对照(自来水)组和氟化钠(100、200 mg/L)、氯化铝(500、1 000 mg/L)单独染毒组及氟化钠+氯化铝联合染毒组,每组4只。采用自由饮水方式进行染毒,母鼠从妊娠第0天至子一代大鼠出生第21天(postnatal day 21,PND21);子一代大鼠于PND90(性成熟)每组随机选取6只(雌∶雄=2∶1)并进行合笼,从其PND22(断乳后)至子二代大鼠PND21继续染毒;每组随机选取子二代8只(雌雄各半),自PND22(断乳后)~PND60(成年)继续染毒。采用酶联免疫吸附法检测海马组织中cAMP蛋白的含量,采用实时荧光定量聚合酶链式反应(qRT-PCR)方法检测海马组织中PKA和CREB mRNA表达水平,采用免疫组织化学方法检测脑组织中PKA和p-CREB蛋白的表达水平。结果氟铝联合染毒对子二代大鼠海马组织中cAMP蛋白的含量和脑组织中PKA、p-CREB蛋白的表达水平及PKA、CREB mRNA的表达水平均存在拮抗作用(P0.05)。结论氟铝联合暴露可能通过抑制子二代大鼠海马cAMP-PKA-CREB信号通路导致学习记忆能力受损,且具有拮抗作用。
[Abstract]:Objective to investigate the effects of continuous exposure during pregnancy and lactation on the signal pathway of cyclic adenosine kinase (cAMP) -protein kinase (cAMP) -cyclic adenosine kinase (A (PKA) -cyclic adenosine kinase (A (PKA) binding protein (CREB) in the hippocampus of the second generation of rats. Methods 36 healthy adult SD pregnant rats of clean grade were randomly divided into 9 groups: control group (tap water), sodium fluoride (100200 mg/L), aluminum chloride (500 mg/L) alone and sodium fluoride combined with aluminum chloride group. There were 4 rats in each group. Free drinking water was used to induce (postnatal day 21 PND21) from day 0 of gestation to day 21 of birth. Six rats (female: male = 2:1) were randomly selected in each group of PND90 (sexual maturation) to be exposed to PND21 from their PND22 (after weaning) to the second generation of rats. 8 offspring (half male and half female) were randomly selected in each group and continued to be poisoned from PND22 (after weaning) to PND60 (adult). The content of cAMP protein in hippocampus was detected by enzyme-linked immunosorbent assay (Elisa), and the expression of PKA and CREB mRNA in hippocampal tissue was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The expression of PKA and p-CREB in brain tissue was detected by immunohistochemical method. Results the level of cAMP protein in hippocampus, the expression level of PKA,p-CREB protein and the expression level of PKA,CREB mRNA in brain tissue of the second generation of rats were antagonized by the combined administration of fluoride and aluminum (P0.05). Conclusion combined exposure of fluoride and aluminum may result in impaired learning and memory ability by inhibiting the cAMP-PKA-CREB signaling pathway in the hippocampus of the second generation of rats and has antagonistic effect.
【作者单位】：贵州医科大学公共卫生学院环境卫生学教研室;
【基金】：国家自然科学基金地区基金(81560519)
【分类号】：R114

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