妊娠期糖尿病患者脂肪组织ERα表达水平对胰岛素抵抗的影响  

Effect of ERα Expression in Adipose Tissue of Gestational Diabetes Mellitus on Insulin Resistance

作　　者：徐宁[1] 张薇[1] Xu Ning;Zhang Wei(Department of Obstetric,Affiliated Hangzhou First People's Hospital,Zhejiang University School of Medicine,Zhejiang 310006,China)

机构地区：[1]浙江大学医学院附属杭州市第一人民医院

出　　处：《医学研究杂志》2019年第11期109-113,共5页Journal of Medical Research

基　　金：浙江省杭州市卫生科技计划医学重点专科专病项目(20150733Q03)

摘　　要：目的通过临床样本和体外实验,研究脂肪组织雌激素受体表达情况与胰岛素抵抗的相关性以及可能的作用机制。方法选择2016年1月~2017年3月在杭州市第一人民医院产检并行择期剖宫产的孕妇为研究对象,其中40例妊娠期糖尿病患者为GDM组,同期41例正常妊娠孕妇作为对照组,于剖宫产手术时收集所有患者皮下、腹膜外及大网膜部位的脂肪组织各两小块,RT-PCR法检测脂肪组织ERαRNA的表达,Western blot法检测ERα蛋白的表达水平。将3T3-L1前脂肪细胞诱导分化为成熟脂肪细胞,给予不同浓度17β-雌二醇(0、0. 1、1、10、100nmol/L)刺激,RT-PCR法测定ERα和GLUT4在成熟脂肪细胞RNA的表达水平,Western blot法检测其在蛋白水平的表达。高浓度17β-雌二醇刺激后Western blot法检测MAPK通路JNK、ERK1/2、P38活性,PI3K/Akt信号通路PI3K、Akt活性。结果 GDM患者组E2水平、HOME-IR明显高于正常妊娠组,差异有统计学意义(P=0. 000)。GDM患者皮下、腹膜外及大网膜3处脂肪组织中,雌激素受体α在RNA和蛋白的表达水平均明显低于正常妊娠患者,差异有统计学意义(P <0. 05)。随着17β-雌二醇浓度的升高,雌激素受体α不论在RNA水平还是在蛋白水平,其表达均逐步受到抑制,并且在10nmol/L浓度下,雌激素受体α表达水平达到最低,差异有统计学意义(P <0. 05),GLUT4的表达情况与ERα相似。结论妊娠期高雌激素水平导致脂肪组织雌激素受体α水平的下降与胰岛素抵抗的发生密切相关。ERα可能通过抑制PI3K/Akt通路和激活JUN通路,加剧了胰岛素抵抗的发生。Objective To study the relationship between estrogen receptor expression in adipose tissue and insulin resistance,and its possible mechanism. Methods From January 2016 to March 2017,40 pregnant women with gestational diabetes mellitus( GDM) were selected as GDM group and 41 normal pregnant women as control group. Subcutaneous,extraperitoneal and greater omentum adipose tissues were collected at the time of caesarean section. The expression of ERα RNA in adipose tissue was detected by RT-PCR and the expression of ERα protein was detected by Western blot. 3 T3-L1 were induced differentiation into mature adipocytes and stimulated with17β-estradiol at different concentrations(0,0. 1,1,10,100 nmol/L). The expression of ERα and GLUT4 in mature adipocytes was measured by RT-PCR method. The protein expression level was detected by Western blot. The activity of JNK,ERK1/2,P38 in MAPK pathway and PI3 K,Akt activity in PI3 K/Akt pathway were detected by Western blot method after high concentration 17β-estradiol stimulation. Results The level of E2 and HOME-IR in GDM group were significantly higher than those in normal pregnancy group( P =0. 000). The expression of ERα in subcutaneous,extraperitoneal and omentum adipose tissues in GDM patients was significantly lower than that in normal pregnant women( P < 0. 05). With the increase of 17β-estradiol concentration,the expression of ERα was gradually inhibited,and the expression of ERα reached the lowest level at the concentration of 10 nmol/L. The difference was statistically significant(P < 0. 05). The expression of GLUT4 was similar to that of ERα. Conclusion The decrease of ERα level in adipose tissue induced by high estrogen level during pregnancy is closely related to the occurrence of insulin resistance. ERα may aggravate the occurrence of insulin resistance by inhibiting PI3 K/Akt pathway and activating JUN pathway.

关 键 词：ERΑ 雌激素受体 胰岛素抵抗 信号通路 

分 类 号：R71[医药卫生—妇产科学]