本文選題：子宮內(nèi)膜癌 + 2型糖尿病��； 參考：《華中科技大學(xué)》2014年博士論文

【摘要】：目的：根據(jù)糖尿病組(db/db小鼠)和正常對(duì)照組(db/m小鼠)子宮內(nèi)膜蛋白質(zhì)差異表達(dá)譜,尋找可能的聯(lián)系肥胖、2型糖尿病及子宮內(nèi)膜癌的紐帶分子。進(jìn)一步,對(duì)篩選出的差異蛋白LDHB,了解其在人子宮內(nèi)膜癌組織中的表達(dá)及臨床意義,再進(jìn)行細(xì)胞水平的功能研究。 方法：采用二維蛋白電泳及蛋白質(zhì)譜檢測(cè)糖尿病組及非糖尿病組小鼠子宮內(nèi)膜的蛋白質(zhì)差異表達(dá)普,并應(yīng)用western及免疫組織化學(xué)方法對(duì)選擇的三個(gè)蛋白進(jìn)行了鑒定。應(yīng)用HE染色方法,比較糖尿病小鼠與非糖尿病小鼠子宮內(nèi)膜的厚度情況。用免疫組織化學(xué)的方法了解LDHB在子宮內(nèi)膜癌中的表達(dá)及臨床意義。采用瞬時(shí)轉(zhuǎn)染shRNA質(zhì)粒的方法,干擾ishikawa中LDHB的表達(dá),檢測(cè)其遷移及侵襲能力的改變。 結(jié)果：糖尿病小鼠與非糖尿病小鼠子宮內(nèi)膜差異蛋白質(zhì)譜中發(fā)現(xiàn)了58個(gè)差異蛋白,其中上調(diào)30個(gè),下調(diào)28個(gè),很多蛋白與線粒體功能相關(guān)。在此基礎(chǔ)上,對(duì)其中的三個(gè)蛋白：LDHB、 CLIC-1和Calbindin鑒定確定三者都在糖尿病小鼠中的表達(dá)高于非糖尿病小鼠。然而,奇怪的是,糖尿病小鼠子宮內(nèi)膜的厚度較對(duì)應(yīng)月份非糖尿病小鼠的子宮內(nèi)膜厚度薄很多,可能是不孕的因素之一。進(jìn)一步,我們發(fā)現(xiàn)在子宮內(nèi)膜癌組織中,LDHB的表達(dá)相對(duì)缺失,基質(zhì)中幾乎無LDHB的表達(dá),LDHB的表達(dá)與肌層浸潤(rùn)深度有關(guān)(P=0.003)。在細(xì)胞水平,干擾LDHB的表達(dá),增加ishikawa細(xì)胞的遷移及侵襲能力(P0.05)。 結(jié)論：糖尿病小鼠子宮內(nèi)膜可能伴隨線粒體功能異常。LDHB在子宮內(nèi)膜癌中表達(dá)相對(duì)缺失,干擾ishikawa細(xì)胞中LDHB的表達(dá)促進(jìn)腫瘤細(xì)胞的遷移和侵襲,子宮內(nèi)膜癌的肌層浸潤(rùn)與LDHB的降低有關(guān)。
[Abstract]:Aim: according to the differential expression profiles of endometrial proteins between diabetic and normal control group (B / r db mice) and normal control group (n = 10), a possible link between obese type 2 diabetes mellitus and endometrial carcinoma was found. Furthermore, the expression and clinical significance of LDHBs in human endometrial carcinoma were investigated, and the function of LDHBs at cell level was studied. Methods: two dimensional protein electrophoresis and protein spectrum were used to detect the differential expression of proteins in endometrium of diabetic and non-diabetic mice. The three proteins were identified by western and immunohistochemistry. The endometrium thickness of diabetic mice and non-diabetic mice was compared by HE staining. To investigate the expression and clinical significance of LDHB in endometrial carcinoma by immunohistochemical method. The transient transfection of shRNA plasmid was used to interfere with the expression of LDHB in ishikawa and to detect the changes of its migration and invasion ability. Results: 58 differentially expressed proteins were found in endometrium of diabetic and non-diabetic mice, including 30 up-regulated proteins and 28 down-regulated proteins. Many proteins were related to mitochondrial function. On this basis, the expression of three of them in diabetic mice was higher than that in non-diabetic mice. Oddly, however, the thickness of the endometrium in diabetic mice is much thinner than that in non-diabetic mice in the corresponding month, which may be one of the factors contributing to infertility. Furthermore, we found that the expression of LDHB was relatively absent in endometrial carcinoma, and almost no expression of LDHB was related to the depth of myometrial invasion. At the cellular level, it interferes with the expression of LDHB and increases the migration and invasion ability of ishikawa cells. Conclusion: the endometrium of diabetic mice may be accompanied by mitochondrial dysfunction. LDHB expression is relatively absent in endometrial carcinoma, which interferes with the expression of LDHB in ishikawa cells and promotes the migration and invasion of tumor cells. The myometrial invasion of endometrial carcinoma is related to the decrease of LDHB.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.33;R587.1

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