当前位置:主页 > 医学论文 > 妇产科论文 >

妊娠糖尿病抑制胎盘AKT-mTOR及SIRT1信号通路

发布时间:2018-04-26 00:23

  本文选题:妊娠期糖尿病 + 胎盘 ; 参考:《重庆医科大学学报》2017年08期


【摘要】:目的:探讨AKT-mTOR信号通路与SIRT1在妊娠期糖尿病(gestational diabetes mellitus,GDM)编程胎儿生长发育中的作用。方法:收集重庆医科大学附属第一医院2014年12月至2015年6月分娩的15例GDM和15例正常产妇的胎盘组织,应用Western blot检测胎盘中AKT-mTOR磷酸化水平与SIRT1的表达水平。以人绒毛外滋养细胞(HTR8/SVneo)体外培养,分为空白对照组、渗透对照组和高糖组。各组处理后使用Western blot检测AKT-mTOR总蛋白和磷酸化水平,以及SIRT1的表达水平,应用流式细胞术(flow cytometry)检测各组的凋亡率。db/+杂合雌鼠妊娠至18.5 d处死后,取其胎盘组织,对其进行基因型鉴定后,选取野生型子代胎盘为GDM组,C57雌鼠胎盘组织为正常对照组,每组各6只。然后应用Western blot检测胎盘组织中AKT-mTOR信号通路。结果:AKT及其下游mTOR磷酸化水平在GDM胎盘中的表达明显低于正常胎盘(0.347±0.031 vs.1.000±0.175,P=0.004;0.465±0.045 vs.1.000±0.098,P=0.000)。同样,GDM组的SIRT1的表达水平也明显低于正常组(0.682±0.055 vs.1.000±0.127,P=0.044);在细胞模型中,经高糖处理后,AKT-mTOR磷酸化水平明显降低(0.512±0.056 vs.1.103±0.111,P=0.023;0.262±0.091 vs.1.153±0.057,P=0.001),而SIRT1的表达同样明显降低(0.472±0.034 vs.1.013±0.098,P=0.040)。高糖组的细胞凋亡率明显升高(14.550±1.624 vs.9.547±0.685,P=0.032)。在动物模型中,GDM组的AKT-mTOR磷酸化水平明显降低(0.527±0.080 vs 1.000±0.055,P=0.003;0.418±0.059 vs.1.000±0.084,P=0.001)。结论:宫内高血糖环境可能通过抑制胎盘AKT-mTOR信号通路,从而编程子代的发育轨迹。
[Abstract]:Objective: to investigate the role of AKT-mTOR signaling pathway and SIRT1 in gestational diabetes mellitusus GDM programming fetal growth and development. Methods: the placental tissues of 15 cases of GDM and 15 cases of normal women were collected from the first affiliated Hospital of Chongqing Medical University from December 2014 to June 2015. The levels of AKT-mTOR phosphorylation and the expression of SIRT1 in placenta were detected by Western blot. Human extracellular trophoblastic cells (HTR 8 / SVneoa) were cultured in vitro and were divided into three groups: blank control group osmotic control group and high glucose group. The total protein and phosphorylation of AKT-mTOR and the expression of SIRT1 were detected by Western blot. The apoptosis rate of each group was detected by flow cytometry. After genotypic identification, the placenta of wild type offspring was selected as the normal control group of C57 female mice in GDM group, with 6 placentas in each group. Then Western blot was used to detect the AKT-mTOR signaling pathway in placenta. Results the expression of mTOR phosphorylation in GDM placenta was significantly lower than that in normal placenta (0.347 卤0.031 vs.1.000 卤0.175 vs.1.000 卤0.465 卤0.045 vs.1.000 卤0.098 vs.1.000 卤0.000). The expression level of SIRT1 in GDM group was significantly lower than that in normal control group (0.682 卤0.055 卤0.127 vs.1.000 卤0.127), and the phosphorylation level of AKT-mTOR was significantly decreased after high glucose treatment (0.512 卤0.056 卤0.111 vs.1.103 卤0.023 卤0.262 卤0.091 vs.1.153 卤0.057 P0. 001), while the expression of SIRT1 was also significantly decreased by 0.472 卤0.034 vs.1.013 卤0.098 P0. 040. The apoptotic rate of high glucose group was significantly increased by 14.550 卤1.624 vs.9.547 卤0.685 vs.9.547 卤0.032%. The level of AKT-mTOR phosphorylation in GDM group was significantly decreased by 0.527 卤0.080 vs 1.000 卤0.055 vs.1.000 卤0.003 卤0.418 卤0.059 vs.1.000 卤0.084 vs.1.000. Conclusion: intrauterine hyperglycemia may be programmed by inhibiting placental AKT-mTOR signaling pathway.
【作者单位】: 重庆医科大学附属第一医院产科重庆医科大学"中国—加拿大—新西兰"联合母胎医学实验室;莱切斯特大学医学院;
【分类号】:R714.256


本文编号:1803650

资料下载
论文发表

本文链接:https://www.wllwen.com/yixuelunwen/fuchankeerkelunwen/1803650.html


Copyright(c)文论论文网All Rights Reserved | 网站地图 |

版权申明:资料由用户f3611***提供,本站仅收录摘要或目录,作者需要删除请E-mail邮箱bigeng88@qq.com