nm23通过PI3K-Akt-mTOR信号通路调节子宫基质细胞蜕膜化

发布时间：2018-06-25 13:21

本文选题：nm23 + 增殖　；参考：《重庆医科大学》2017年硕士论文

【摘要】：目的:成功的胚胎着床依赖于有良好活性的胚泡和处于容受态的子宫二者间的相互作用,在这一过程中母体子宫内膜涉及到一系列基因和信号通路的表达和变化。nm23是最早发现的抑制细胞迁移的基因,参与细胞各种生理过程,例如增殖、分化。为了探究nm23在胚胎着床中的调控作用,我们应用免疫组织化学技术、Western Blot、RT-q PCR研究nm23基因在早孕小鼠模型,假孕小鼠模型的表达规律;检测nm23基因在人的子宫内膜组织及蜕膜组织中的表达模式;通过体内和体外人工诱导蜕膜化研究nm23在基质细胞蜕膜化过程中的调控作用;利用体外激素模型验证激素对nm23的调节作用;并借助基质细胞体外功能试验进一步探究PI3K-Akt-mTOR信号通路在nm23调控的蜕膜化过程中的作用。方法:(1)应用免疫组织化学技术,Western blot及RT-q PCR检测nm23在早孕小鼠模型和假孕小鼠模型中的表达规律。(2)应用免疫组织化学技术及Western blot检测nm23在正常人子宫内膜组织以及蜕膜组织中的表达规律。(3)通过体内及体外人工诱导蜕膜化实验,探讨nm23在子宫内膜基质细胞的蜕膜化的调控作用。(4)利用分离的原代小鼠子宫基质细胞和人的子宫基质细胞系建立体外激素模型探讨激素对nm23是否有调节作用。(5)通过基质细胞体外功能试验检测nm23在蜕膜化过程中的潜在机制。结果:(1)nm23-m1在早孕小鼠模型中主要表达在蜕膜区,其在假孕小鼠模型的表达模式与早孕小鼠模型相似。(2)在人的子宫组织表达模式中,相对于增生期和分泌期子宫内膜组织,nm23-h1在蜕膜组织中呈高表达。(3)nm23-m1在体内人工诱导蜕膜化组织表达升高,并且,si-nm23可以显著降低基质细胞的增殖和分化进而来影响蜕膜化过程。(4)小鼠和人的基质细胞激素模型证明雌激素和孕激素对nm23基因有调节作用。(5)PI3K-Akt-mTOR信号通路参与nm23调控的子宫内膜基质细胞蜕膜化过程。结论:nm23可通过PI3K-Akt-mTOR信号通路调节基质细胞的蜕膜化过程。
[Abstract]:Objective: successful embryo implantation depends on the interaction between a well-active blastocyst and a receptive uterus. During this process, maternal endometrium is involved in a series of genes and signal pathway expression and changes. Nm23 is the first discovered gene to inhibit cell migration, involved in various physiological processes of cell, such as proliferation and differentiation. In order to investigate the regulation of nm23 in embryo implantation, we used immunohistochemical technique to study the expression of nm23 gene in mouse model of early pregnancy and pseudopregnant mouse model. The expression pattern of nm23 gene in human endometrial tissue and decidua tissue was detected, and the regulation of nm23 in decidualization of stromal cells was studied by in vivo and in vitro induced decidualization. In vitro hormone model was used to verify the regulatory effect of hormone on nm23, and the role of PI3K-Akt-mTOR signaling pathway in decidualization regulated by nm23 was further explored by stromal cell function test in vitro. Methods: (1) Immunohistochemical technique was used to detect the expression of nm23 in early pregnant mice and pseudopregnant mice. (2) Immunohistochemical technique and Western blot were used to detect the expression of nm23 in normal endometrium. (3) artificial induced decidualization in vivo and in vitro, To investigate the regulation of nm23 on decidualization of endometrial stromal cells. (4) to establish an in vitro hormone model using isolated primary mouse stromal cells and human stromal cell lines to investigate whether hormones can regulate nm23. The potential mechanism of nm23 in decidualization was detected by in vitro function test of stromal cells. Results: (1) the expression of nm23-m1 was mainly in decidual region in early pregnant mice, and the expression pattern in pseudopregnancy mice was similar to that in early pregnancy mice. (2) in human uterine tissues, the expression pattern of nm23-m1 was similar to that in early pregnancy mice. The expression of nm23-h1 in decidua tissue was higher than that in proliferative and secretory endometrium. (3) the expression of nm23-h1 was increased in decidualized tissue induced by nm23-m1 in vivo. In addition, PI3K-Akt-mTOR signaling pathway is involved in the regulation of nm23 gene. (4) the mouse and human stromal cell hormone models demonstrate that estrogen and progesterone can regulate nm23 gene. (5) PI3K-Akt-mTOR signaling pathway is involved in the regulation of nm23. Controlled decidualization of endometrial stromal cells. Conclusion:% nm23 can regulate the decidualization of stromal cells through PI3K-Akt-mTOR signaling pathway.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R714

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