孕期咖啡因暴露所致雌性子代胎鼠肾脏宫内发育迟缓及其发生机制

孕期咖啡因暴露所致雌性子代胎鼠肾脏宫内发育迟缓及其发生
机制
万阳;敖英;李斌;熊颖;孙朝霞;胡霜霜;汪晖
【期刊名称】《中国药理学通报》
【年(卷),期】2018(34)2
【摘要】Aim To explore the effects of prenatal caf-feine exposure (PCE) on fetal renal growth retardation and corticosterone on the gene expression of metanephric mesenchyme stem cells.Methods Pregnant Wistar rats were administered with caffeine (30,120 mg ·kg-1) from gestational day 9 to 20.Female fetal kidney samples were collected for morphological observation and gene expression examination.The metanephric mesenchyme stem cells were harvested for cell culture,and renal related genes were detected after the treatment of corticosterone with different concentrations (250,500,1 000 μg · L-1) for 24 hours.Results Compared with the control group,the fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft,accompanied with the repression of the gene expression of glial-cell-line-derived neurotrophic factor/tyrosine kinase receptor (GDNF/c-Ret) signaling pathway.The GDNF/c-Ret sig naling pathway and angiotensin Ⅱ receptor type 1 (AT1R)/AT2R expression of metanephric mesenchyme stem cells also decreased in corticosterone groups.Conclusions PCE may induce dysplasia of female fetal kidneys.The potential mechanism is related to the
repression of the gene expression of AT1R/AT2R and GDNF/c-Ret signaling pathway by PCE mediated by corticosterone in utero.%目的观察孕期咖啡因暴露(PCE)♀胎肾发育病理学变化和皮质酮(CORT)处理对原代后肾间充质细胞基因表达的影响,探究PCE影响胎鼠肾脏发育的可能机制.方法受孕Wistar 大鼠于孕9-20 d(GD 9-20)经口灌胃咖啡因(30、120mg·kg-1·d-1),孕鼠于GD20处死,取♀胎鼠并收集肾脏,检测肾脏病理学变化和基因表达;在原代后肾间充质细胞上给予不同浓度CORT(250、500、1 000 μg·L-1)处理24 h,检测细胞基因表达.结果与对照组相比,PCE组♀胎肾肾小球的球囊空虚,鲍曼囊腔变大,毛细血管网发育不良,GDNF/c-Ret信号通路抑制;CORT处理原代后肾间充质细胞下调AT1R/AT2 R 及GDNF/c-Ret信号通路的表达.结论 PCE♀胎鼠肾脏发育不良,其机制与PCE所致高血CORT下胎肾局部AT1R/AT2R及GDNF/c-Ret信号通路的表达抑制有关.【总页数】7页(P213-219)
【作者】万阳;敖英;李斌;熊颖;孙朝霞;胡霜霜;汪晖
【作者单位】武汉大学基础医学院药理学系,湖北武汉430071;武汉大学基础医学院药理学系,湖北武汉430071;武汉大学发育源性疾病湖北省重点实验室,湖北武汉430071;武汉大学中南医院骨科,湖北武汉430071;武汉大学基础医学院药理学系,湖北武汉430071;武汉大学基础医学院药理学系,湖北武汉430071;武汉大学基础医学院药理学系,湖北武汉430071;武汉大学基础医学院药理学系,湖北武汉430071;武汉大学发育源性疾病湖北省重点实验室,湖北武汉430071
【正文语种】中文
【中图分类】R-332;R322.61;R329.24;R392.11;R714.51;R971.7;R977.11
【相关文献】
1.大鼠孕期尼古丁暴露致成年雌性子代抑郁症易感机制研究 [J], 余樱;石昭坤;徐丹;张兆辉;汪晖
2.孕期咖啡因暴露导致子代成年雌性大鼠代谢综合征易感及发生机制 [J], 裴林国;张郦;鄢友娥;夏利平;徐丹;汪晖
3.孕期咖啡因暴露的雄性子代大鼠高脂饮食/慢性应激下糖代谢异常及胰岛素抵抗的发生 [J], 周瑾;寇皓;郭喻;张郦;汪晖
4.孕期咖啡因暴露所致子代HPA轴高应激敏感性增加高脂饮食下胰岛素抵抗发生的风险 [J], 张郦;汪晖
5.11β-HSD2低表达编程增加孕期咖啡因暴露所致子代大鼠海马发育损伤易感 [J], 焦哲潇;胡泽文;郭自景;徐丹;汪晖
因版权原因，仅展示原文概要，查看原文内容请购买。