白血病抑制因子及蛋白激酶B在子宫内膜息肉发生中的作用

发布时间：2018-03-30 15:58

本文选题：白血病抑制因子　切入点：蛋白激酶B　出处：《河北医科大学》2014年硕士论文

【摘要】：目的：子宫内膜息肉是子宫内膜常见病变之一，，发病率高达25%，常见于围绝经期和绝经后妇女；高龄、晚绝经、肥胖、糖尿病、他莫西芬治疗等均是其发生的危险因素。目前针对子宫内膜息肉的诊断主要依靠超声影像学及宫腔镜检查，治疗以宫腔镜下切除为主。随着子宫内膜息肉的发病率越来越高，恶变率也有所增加，其病因研究日益重要。子宫内膜息肉的病因研究很多，从炎症、激素及其受体、细胞分子及细胞增殖凋亡调控到免疫因素等方面较为广泛。细胞因子(cytokine)是指主要由免疫细胞分泌的、能调节细胞功能的小分子多肽。在免疫应答过程中，细胞因子对于细胞间相互作用、细胞的生长和分化有重要调节作用。子宫内膜组织有多种细胞因子的表达，如表皮细胞生长因子(EGF)、胰岛素样生长因子(IGF)、血管内皮细胞生长因子(VEGF)等，通过特定的内分泌途径作用于子宫内膜组织，它们的分泌及表达调控着子宫内膜的组织病变。白血病抑制因子(Leukemia inhibitor factor，LIF)是一种多效性的细胞生长因子，在人类生殖和内分泌中可能扮演着重要角色。LIF能够调节细胞的增殖、分化和表型，抑制脂蛋白脂酶活性。蛋白激酶B又称PKB，即Akt，是一种丝氨酸/苏氨酸蛋白激酶，在细胞存活和凋亡中起重要作用。胰岛素等生长和存活因子(IGF)都可以激活Akt信号(PI3K/Akt)途径。LIF及Akt是细胞因子中关系细胞增长、细胞增殖与凋亡的相关蛋白质因子，它们在很多细胞中均有表达，且与多种良恶性疾病关系密切，它们影响并调控着细胞的数量及质量，在良性增生性疾病及恶性肿瘤中起着至关重要的作用。本研究通过检测子宫内膜息肉组中LIF及Akt含量的变化，对比正常对照组，并结合临床资料，分析LIF及Akt与子宫内膜息肉发生发展的关系，为临床治疗与预防息肉复发提供新的思路。方法：应用Western blot方法检测子宫内膜息肉及正常子宫内膜组织中LIF及Akt的表达，并观察绝经前与绝经后组间有无差异，观察两个指标之间有无一定联系。结果： 1绝经前后子宫内膜息肉临床特点的比较绝经前息肉直径为1.43±0.55cm，绝经后直径为1.24±0.45cm，根据t检验息肉的大小并无明显差别(P0.05)。绝经前患者与绝经后患者息肉发生数目有所不同，绝经前单发14例，多发18例，绝经后单发23例，多发3例。经卡方检验其差异有统计学意义(P0.05)。表明绝经前子宫内膜息肉易多发，绝经后则易单发。 2LIF，Akt在子宫内膜息肉组织中的表达及与临床资料的关系 LIF，Akt在子宫内膜息肉组及正常子宫内膜组织中的蛋白条带灰度值分别为1.317±0.210，0.929±0.202和1.147±0.175，0.812±0.184，差异均具有统计学意义(P0.05，P0.05)，可见LIF，Akt在子宫内膜息肉组织中的表达明显高于正常内膜组织。以绝经前后分组，LIF，Akt在绝经前与绝经后子宫内膜息肉中的表达无明显差异。以子宫息肉的直径分组，为使数据的准确，息肉的直径测量选择单发息肉。在58例子宫内膜息肉患者中，37例为单发。根据直径大小划分为小于1.5cm、大于及等于1.5cm两组。LIF在两组中的表达为，1.204±0.140,1.405±0.210； Akt在两组中的表达为1.079±0.130,1.218±0.184，经t检验及非参数检验，差异均具有统计学意义(P0.05，P0.05)，表明LIF及Akt的表达与子宫内膜息肉的直径大小有关，息肉越大，息肉组织中LIF及Akt的含量越高。 3LIF与Akt的相关性根据Pearson相关系数分析，LIF与Akt的相关系数r=0.772，并且相关性具有统计学意义(P0.05)。结论： 1绝经前子宫内膜息肉好多发，绝经后好单发，且绝经前后子宫内膜息肉患者的子宫内膜息肉大小无明显差异。 2子宫内膜息肉组织中LIF，Akt表达量明显高于正常内膜组织，提示子宫内膜息肉的发生可能与二者相关。 3LIF及Akt可能参与了子宫内膜息肉的恶变过程。 4LIF/PI3K/Akt通路可能存在于子宫内膜息肉发生中。
[Abstract]:Objective : The endometrial polyps are one of the most common pathological changes in the endometrium , the morbidity rate is as high as 25 % , which is common in perimenopausal and postmenopausal women .
In the elderly , late menopause , obesity , diabetes , tamoxifen therapy , etc . are all the risk factors . The diagnosis of endometrial polyps mainly depends on ultrasound imaging and hysteroscopy . The etiology of endometrial polyps is more and more important . The etiology of endometrial polyps is much more important .

cytokine is a small molecule polypeptide which is secreted by immune cells and capable of regulating cell function . During the immune response , the cytokine plays an important role in cell - cell interaction , cell growth and differentiation . The endometrial tissue has various cytokines such as epidermal cell growth factor ( EGF ) , insulin - like growth factor ( IGF ) , vascular endothelial growth factor ( VEGF ) , etc . , and acts on the endometrium tissue through specific endocrine pathways , and their secretion and expression regulate the tissue pathological changes of the endometrium .

Leukemia inhibitory factor ( LIF ) is a kind of multipotent cell growth factor which plays an important role in human reproduction and endocrine . LIF can regulate cell proliferation , differentiation and phenotype , inhibit lipoprotein lipase activity . Protein kinase B , also known as PKB , is a kind of serine / threonine protein kinase , which plays an important role in cell survival and apoptosis .

In order to provide a new idea for the clinical treatment and prevention of polyp recurrence , the relationship between LIF and the content change of MMP - 3 in the endometrial polyps was detected by comparing with the normal control group and clinical data .

Methods : Using Western blot to detect LIF in endometrial polyps and normal endometrium , and observe whether there was any difference between the premenopausal and postmenopausal women , and observe whether there was a certain association between the two indexes .

Results :

Comparison of clinical characteristics of endometrial polyps before and after menopause

There was no significant difference between premenopausal and postmenopausal women ( P 0.05 ) . The number of polyps in premenopausal patients was different from that before menopause ( P0.05 ) .

Expression and clinical data of 2LIF and 3 - 3 in endometrial polyps

The gray values of protein bands in endometrial polyps and normal endometrium were 1.317 卤 0.210 , 0.929 卤 0.202 and 1.147 卤 0.175 , 0.812 卤 0.184 , respectively .

In 58 cases of endometrial polyps , 37 cases were single hair . In 58 cases of endometrial polyps , 37 cases were single . LIF was divided into two groups with diameter size of less than 1.5 cm , greater than or equal to 1.5cm . LIF was 1.204 卤 0.140 , 1.405 卤 0.210 in both groups .
There was a statistically significant difference ( P 0.05 , P 0 . 05 ) between the two groups ( P 0.05 , P 0 . 05 ) . The higher the expression of LIF , and the size of the endometrial polyps , the greater the polyp , the higher the LIF in the polyp tissue and the higher the content of the protein .

Correlation between 3LIF and akt

According to Pearson correlation coefficient , the correlation coefficient r = 0.772 , and the correlation was statistically significant ( P0.05 ) .

CsA could cause PLT to decrease ;

There was no significant difference in the size of endometrial polyps in patients with endometrial polyps before and after menopause .

The expression of LIF in endometrial polyps was significantly higher than that of normal endometrium , suggesting that the occurrence of endometrial polyps might be related to both .

3LIF and 3 - LIF may be involved in the malignant process of endometrial polyps .

The 4LIF / PI3 pathway may exist in the occurrence of endometrial polyps .

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R711.74

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