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  

Effects of continuous exposure to fluoride combined with aluminum during gestation and lactation periods on the cAMP-PKA-CREB signaling pathway in the offsprings' hippocampus

作　　者：吴宇[1] 张华[1] 谢春[1] 杨小雪[1] 陈媛[1] 葛启迪 

机构地区：[1]贵州医科大学公共卫生学院环境卫生学教研室,贵州贵阳550004

出　　处：《环境与健康杂志》2015年第12期1072-1075,共4页Journal of Environment and Health

基　　金：国家自然科学基金地区基金(81560519)

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（P〈0.05）。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。Objective To explore the effects of the continuous exposure to fluoride combined with aluminum during gestation and lactation periods on the cAMP-PKA-CREB signaling pathway in the offsprings＇ hippocampus. Methods Thirty-six pregnant rats were randomly divided into control and experimental groups as follows, control group（drinking tap water）, fluoride group（drinking the water containing sodium fluoride of 100 mg/L and 200 mg/L）, aluminum group（drinking the water containing aluminum chloride of 500 mg/L and 1 000 mg/L）, fluoride plus aluminum group,four in each. The pregnant rats were treated with fluoride or aluminum through drinking water freely from pregnant day 0 to postnatal day 21 of the first generation rats（PND21）. And six offspring rats were selected randomly in each group and were mated according to 2 ∶1 when the first generation rats were at PND90. And eight second generation offspring rats were selected randomly in each group and were weighed with an interval of one week. The pups were given the same treatment as their parental generation. The protein content of cAMP and protein expression levels of PKA and mRNA expression levels of PKA and CREB and phosphorylated CREB（pCREB） were detected by ELISA,real-time polymerase chain reaction and immunohistochemistry respectively. Results Fluoride exposure combined with aluminum had antagonistic interaction on the protein content of cAMP and protein expression levels of PKA andp-CREB and mRNA expression levels of PKA and CREB（P0.05）. Conclusion The continuous exposure to fluoride combined with aluminum may affect learning and memory of rats through inhibiting on c AMP-PKA-CREB signaling pathway and the effect is antagonistic.

关 键 词：氟 铝 环磷酸腺苷 蛋白激酶A 环磷酸腺苷反应元件结合蛋白 

分 类 号：R994.6[医药卫生—毒理学]