本文選題：白血病抑制因子　切入點(diǎn)：蛋白激酶B　出處：《河北醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：子宮內(nèi)膜息肉是子宮內(nèi)膜常見(jiàn)病變之一，，發(fā)病率高達(dá)25%，常見(jiàn)于圍絕經(jīng)期和絕經(jīng)后婦女；高齡、晚絕經(jīng)、肥胖、糖尿病、他莫西芬治療等均是其發(fā)生的危險(xiǎn)因素。目前針對(duì)子宮內(nèi)膜息肉的診斷主要依靠超聲影像學(xué)及宮腔鏡檢查，治療以宮腔鏡下切除為主。隨著子宮內(nèi)膜息肉的發(fā)病率越來(lái)越高，惡變率也有所增加，其病因研究日益重要。子宮內(nèi)膜息肉的病因研究很多，從炎癥、激素及其受體、細(xì)胞分子及細(xì)胞增殖凋亡調(diào)控到免疫因素等方面較為廣泛。 細(xì)胞因子(cytokine)是指主要由免疫細(xì)胞分泌的、能調(diào)節(jié)細(xì)胞功能的小分子多肽。在免疫應(yīng)答過(guò)程中，細(xì)胞因子對(duì)于細(xì)胞間相互作用、細(xì)胞的生長(zhǎng)和分化有重要調(diào)節(jié)作用。子宮內(nèi)膜組織有多種細(xì)胞因子的表達(dá)，如表皮細(xì)胞生長(zhǎng)因子(EGF)、胰島素樣生長(zhǎng)因子(IGF)、血管內(nèi)皮細(xì)胞生長(zhǎng)因子(VEGF)等，通過(guò)特定的內(nèi)分泌途徑作用于子宮內(nèi)膜組織，它們的分泌及表達(dá)調(diào)控著子宮內(nèi)膜的組織病變。 白血病抑制因子(Leukemia inhibitor factor，LIF)是一種多效性的細(xì)胞生長(zhǎng)因子，在人類生殖和內(nèi)分泌中可能扮演著重要角色。LIF能夠調(diào)節(jié)細(xì)胞的增殖、分化和表型，抑制脂蛋白脂酶活性。蛋白激酶B又稱PKB，即Akt，是一種絲氨酸/蘇氨酸蛋白激酶，在細(xì)胞存活和凋亡中起重要作用。胰島素等生長(zhǎng)和存活因子(IGF)都可以激活A(yù)kt信號(hào)(PI3K/Akt)途徑。LIF及Akt是細(xì)胞因子中關(guān)系細(xì)胞增長(zhǎng)、細(xì)胞增殖與凋亡的相關(guān)蛋白質(zhì)因子，它們?cè)诤芏嗉?xì)胞中均有表達(dá)，且與多種良惡性疾病關(guān)系密切，它們影響并調(diào)控著細(xì)胞的數(shù)量及質(zhì)量，在良性增生性疾病及惡性腫瘤中起著至關(guān)重要的作用。 本研究通過(guò)檢測(cè)子宮內(nèi)膜息肉組中LIF及Akt含量的變化，對(duì)比正常對(duì)照組，并結(jié)合臨床資料，分析LIF及Akt與子宮內(nèi)膜息肉發(fā)生發(fā)展的關(guān)系，為臨床治療與預(yù)防息肉復(fù)發(fā)提供新的思路。 方法：應(yīng)用Western blot方法檢測(cè)子宮內(nèi)膜息肉及正常子宮內(nèi)膜組織中LIF及Akt的表達(dá)，并觀察絕經(jīng)前與絕經(jīng)后組間有無(wú)差異，觀察兩個(gè)指標(biāo)之間有無(wú)一定聯(lián)系。 結(jié)果： 1絕經(jīng)前后子宮內(nèi)膜息肉臨床特點(diǎn)的比較 絕經(jīng)前息肉直徑為1.43±0.55cm，絕經(jīng)后直徑為1.24±0.45cm，根據(jù)t檢驗(yàn)息肉的大小并無(wú)明顯差別(P0.05)。絕經(jīng)前患者與絕經(jīng)后患者息肉發(fā)生數(shù)目有所不同，絕經(jīng)前單發(fā)14例，多發(fā)18例，絕經(jīng)后單發(fā)23例，多發(fā)3例。經(jīng)卡方檢驗(yàn)其差異有統(tǒng)計(jì)學(xué)意義(P0.05)。表明絕經(jīng)前子宮內(nèi)膜息肉易多發(fā)，絕經(jīng)后則易單發(fā)。 2LIF，Akt在子宮內(nèi)膜息肉組織中的表達(dá)及與臨床資料的關(guān)系 LIF，Akt在子宮內(nèi)膜息肉組及正常子宮內(nèi)膜組織中的蛋白條帶灰度值分別為1.317±0.210，0.929±0.202和1.147±0.175，0.812±0.184，差異均具有統(tǒng)計(jì)學(xué)意義(P0.05，P0.05)，可見(jiàn)LIF，Akt在子宮內(nèi)膜息肉組織中的表達(dá)明顯高于正常內(nèi)膜組織。 以絕經(jīng)前后分組，LIF，Akt在絕經(jīng)前與絕經(jīng)后子宮內(nèi)膜息肉中的表達(dá)無(wú)明顯差異。以子宮息肉的直徑分組，為使數(shù)據(jù)的準(zhǔn)確，息肉的直徑測(cè)量選擇單發(fā)息肉。在58例子宮內(nèi)膜息肉患者中，37例為單發(fā)。根據(jù)直徑大小劃分為小于1.5cm、大于及等于1.5cm兩組。LIF在兩組中的表達(dá)為，1.204±0.140,1.405±0.210； Akt在兩組中的表達(dá)為1.079±0.130,1.218±0.184，經(jīng)t檢驗(yàn)及非參數(shù)檢驗(yàn)，差異均具有統(tǒng)計(jì)學(xué)意義(P0.05，P0.05)，表明LIF及Akt的表達(dá)與子宮內(nèi)膜息肉的直徑大小有關(guān)，息肉越大，息肉組織中LIF及Akt的含量越高。 3LIF與Akt的相關(guān)性 根據(jù)Pearson相關(guān)系數(shù)分析，LIF與Akt的相關(guān)系數(shù)r=0.772，并且相關(guān)性具有統(tǒng)計(jì)學(xué)意義(P0.05)。 結(jié)論： 1絕經(jīng)前子宮內(nèi)膜息肉好多發(fā)，絕經(jīng)后好單發(fā)，且絕經(jīng)前后子宮內(nèi)膜息肉患者的子宮內(nèi)膜息肉大小無(wú)明顯差異。 2子宮內(nèi)膜息肉組織中LIF，Akt表達(dá)量明顯高于正常內(nèi)膜組織，提示子宮內(nèi)膜息肉的發(fā)生可能與二者相關(guān)。 3LIF及Akt可能參與了子宮內(nèi)膜息肉的惡變過(guò)程。 4LIF/PI3K/Akt通路可能存在于子宮內(nèi)膜息肉發(fā)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 鹵 0.210 , 0.929 鹵 0.202 and 1.147 鹵 0.175 , 0.812 鹵 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 鹵 0.140 , 1.405 鹵 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 .

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R711.74

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