本文選題：妊娠期糖尿病 + 胎盤��； 參考：《重慶醫(yī)科大學學報》2017年08期

【摘要】：目的:探討AKT-mTOR信號通路與SIRT1在妊娠期糖尿病(gestational diabetes mellitus,GDM)編程胎兒生長發(fā)育中的作用。方法:收集重慶醫(yī)科大學附屬第一醫(yī)院2014年12月至2015年6月分娩的15例GDM和15例正常產(chǎn)婦的胎盤組織,應用Western blot檢測胎盤中AKT-mTOR磷酸化水平與SIRT1的表達水平。以人絨毛外滋養(yǎng)細胞(HTR8/SVneo)體外培養(yǎng),分為空白對照組、滲透對照組和高糖組。各組處理后使用Western blot檢測AKT-mTOR總蛋白和磷酸化水平,以及SIRT1的表達水平,應用流式細胞術(flow cytometry)檢測各組的凋亡率。db/+雜合雌鼠妊娠至18.5 d處死后,取其胎盤組織,對其進行基因型鑒定后,選取野生型子代胎盤為GDM組,C57雌鼠胎盤組織為正常對照組,每組各6只。然后應用Western blot檢測胎盤組織中AKT-mTOR信號通路。結果:AKT及其下游mTOR磷酸化水平在GDM胎盤中的表達明顯低于正常胎盤(0.347±0.031 vs.1.000±0.175,P=0.004;0.465±0.045 vs.1.000±0.098,P=0.000)。同樣,GDM組的SIRT1的表達水平也明顯低于正常組(0.682±0.055 vs.1.000±0.127,P=0.044);在細胞模型中,經(jīng)高糖處理后,AKT-mTOR磷酸化水平明顯降低(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的表達同樣明顯降低(0.472±0.034 vs.1.013±0.098,P=0.040)。高糖組的細胞凋亡率明顯升高(14.550±1.624 vs.9.547±0.685,P=0.032)。在動物模型中,GDM組的AKT-mTOR磷酸化水平明顯降低(0.527±0.080 vs 1.000±0.055,P=0.003;0.418±0.059 vs.1.000±0.084,P=0.001)。結論:宮內(nèi)高血糖環(huán)境可能通過抑制胎盤AKT-mTOR信號通路,從而編程子代的發(fā)育軌跡。
[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 鹵0.031 vs.1.000 鹵0.175 vs.1.000 鹵0.465 鹵0.045 vs.1.000 鹵0.098 vs.1.000 鹵0.000). The expression level of SIRT1 in GDM group was significantly lower than that in normal control group (0.682 鹵0.055 鹵0.127 vs.1.000 鹵0.127), and the phosphorylation level of AKT-mTOR was significantly decreased after high glucose treatment (0.512 鹵0.056 鹵0.111 vs.1.103 鹵0.023 鹵0.262 鹵0.091 vs.1.153 鹵0.057 P0. 001), while the expression of SIRT1 was also significantly decreased by 0.472 鹵0.034 vs.1.013 鹵0.098 P0. 040. The apoptotic rate of high glucose group was significantly increased by 14.550 鹵1.624 vs.9.547 鹵0.685 vs.9.547 鹵0.032%. The level of AKT-mTOR phosphorylation in GDM group was significantly decreased by 0.527 鹵0.080 vs 1.000 鹵0.055 vs.1.000 鹵0.003 鹵0.418 鹵0.059 vs.1.000 鹵0.084 vs.1.000. Conclusion: intrauterine hyperglycemia may be programmed by inhibiting placental AKT-mTOR signaling pathway.
【作者單位】： 重慶醫(yī)科大學附屬第一醫(yī)院產(chǎn)科重慶醫(yī)科大學"中國—加拿大—新西蘭"聯(lián)合母胎醫(yī)學實驗室;萊切斯特大學醫(yī)學院;
【分類號】：R714.256
，

本文編號：1803650