Gestational diabetes mellitus impairs AKT-mTOR and SIRT1 signaling pathways in placenta

Zhang Li; Yu Xingyang; Xu Ping; Philip N.Baker; Qi Hongbo; Tong Chao; Zhang Hua

doi:10.13406/j.cnki.cyxb.001250

您当前的位置：

首页 >

文章列表页 >

Gestational diabetes mellitus impairs AKT-mTOR and SIRT1 signaling pathways in placenta

更新时间：2024-01-17

- Gestational diabetes mellitus impairs AKT-mTOR and SIRT1 signaling pathways in placenta
- Journal of Chongqing Medical University Vol. 42, Issue 8, Pages: 1023-1028(2017)
- 作者机构：
  
  1. 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
  2. 莱切斯特大学医学院
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.001250
  CLC： R714.256
- Published：2017，
扫描看全文
[1]张莉,余昕烊,徐萍,Philip N.Baker,漆洪波,童超,张华.妊娠糖尿病抑制胎盘AKT-mTOR及SIRT1信号通路[J].重庆医科大学学报,2017,42(08):1023-1028.

Zhang Li, Yu Xingyang, Xu Ping, et al. Gestational diabetes mellitus impairs AKT-mTOR and SIRT1 signaling pathways in placenta. [J]. Journal of Chongqing Medical University 42(8):1023-1028(2017)
[1]张莉,余昕烊,徐萍,Philip N.Baker,漆洪波,童超,张华.妊娠糖尿病抑制胎盘AKT-mTOR及SIRT1信号通路[J].重庆医科大学学报,2017,42(08):1023-1028. DOI： 10.13406/j.cnki.cyxb.001250.

Zhang Li, Yu Xingyang, Xu Ping, et al. Gestational diabetes mellitus impairs AKT-mTOR and SIRT1 signaling pathways in placenta. [J]. Journal of Chongqing Medical University 42(8):1023-1028(2017) DOI： 10.13406/j.cnki.cyxb.001250.

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 explore the role of AKT-mTOR signaling pathway and SIRT1 in fetal growth and development programming of gestational diabetes mellitus(GDM). Methods:Fifteen cases of GDM and 15 cases of normal maternal placental tissue were collected in the First Affiliated Hospital of Chongqing Medical University from December 2014 to June 2015. Western blot was used to detect the expression of AKT-mTOR and SIRT1 in human placenta. Human transformed primary extravillous trophoblast cell line(HTR8/SVneo)cells were used to establish the model of GDM

which were divided into normal group

osmotic control

and high glucose group.After the treatment

the expressions of AKT-mTOR and SIRT1 were detected by Western blot;Flow cytometry was used to detect the apoptosis rate in each group. On day 18.5 of gestation

db/+ mice were anesthetized with pentobarbitone and a caesarean section was performed. The placentas were excised and frozen immediately for genotyping

and then the wild type placentas were selected for GDM group. C57 mice placentas were control group(normal). Then the expressions of AKT-mTOR were detected by Western blot.Results:The phosphorylation of AKT and mTOR in placenta of GDM group was significantly lower than that of normal group(0.347±0.031 vs. 1.000±0.175

P=0.004;0.465±0.045 vs.1.000±0.098

P=0.000). Similarly

the expression of SIRT1 was obviously decreased in GDM group than in normal group(0.682±0.055 vs. 1.000±0.127

P=0.044). In the cell model

high glucose could decrease AKT and mTOR phosphorylation(0.512±0.056 vs. 1.103±0.111

P=0.023;0.262±0.091 vs. 1.153±0.057

P=0.001)and SIRT1 expression(0.472±0.034 vs. 1.013±0.098

P=0.040). The apoptosis rate in high glucose group was significantly increased than that in normal group(14.550±1.624 vs.9.547±0.685

P=0.032). In the animal model

the phosphorylation of AKT and mTOR also was significantly decreased in GDM group(0.527±0.080 vs. 1.000±0.055

P=0.003;0.418±0.059 vs. 1.000±0.084

P=0.001). Conclusion:The intrauterine environment of high glucose may inhibit placental AKT-mTOR signaling pathways

thereby programming offspring development track.

关键词

妊娠期糖尿病胎盘AktmTORSIRT1

Keywords

gestational diabetes mellitusplacentaAktmTORSIRT1

references

Views

262

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Application of carbohydrate counting in blood glucose control among gestational diabetes patients

The relationship between GH-IGF-I system and IUGR

Placenta accreta: report of twelve cases and review of literature

Leptin-mRNA expression in placental tissues:relationship with fetal growth and development

The experimental study on phosphatidylinositol 3-kinase/Akt in neural stem cells in vitro

Related Author

Cheng Qingfeng

Zan Liping

Liao Kun

Hu Chunjuan

Liu Xiurong

Fu Shimin

Liu Zhiping

Li Feifei

Related Institution

Department of Endocrinology,The First Affiliated Hospital of Chongqing Medical University

重庆医科大学医学超声工程研究所

西安交通大学第一临床医学院

The Institute of Ultrasonic Engineering in Medicine,Chongqing Medical University

⁰