本文選題：子宮內(nèi)膜異位癥 + VCAM-1��； 參考：《浙江大學(xué)》2017年碩士論文

【摘要】：研究背景:子宮內(nèi)膜異位癥(簡稱內(nèi)異癥,endometriosis,EMs)在育齡期婦女中發(fā)病率高達(dá)10%～15%,近年來發(fā)病率有上升趨勢。它是指具有生長能力的子宮內(nèi)膜異位至子宮腔被覆內(nèi)膜及宮體肌層以外的組織,常常伴有慢性盆腔痛、痛經(jīng)、不孕等,目前發(fā)病機(jī)制仍未完全明確。子宮內(nèi)膜異位癥是一種良性疾病,卻在侵襲、新生血管生成、增殖、凋亡等諸多方面與惡性腫瘤有極大相似性�，F(xiàn)有的研究已經(jīng)發(fā)現(xiàn)了 EMs患者腹腔內(nèi)環(huán)境中的免疫細(xì)胞、細(xì)胞因子的變化,認(rèn)為免疫機(jī)制異常在EMs的發(fā)生、發(fā)展過程中起著重要作用。子宮內(nèi)膜腺上皮及基底膜均有多種細(xì)胞粘附分子(cell adhesion molecules,CAMs)的表達(dá),越來越多的研究已證實(shí)某些CAMs的異常表達(dá)可能參與了 EMs的侵襲、粘附及種植過程。血管細(xì)胞粘附分子(vascular cell adhesion molecule 1,VCAM-1)和細(xì)胞間粘附分子(intercellular adhesion molecule 1,ICAM-1)是免疫球蛋白超家族家族中的兩個(gè)重要成員,均為跨膜糖蛋白粘附分子,前者主要分布在激活的內(nèi)皮細(xì)胞、樹突狀細(xì)胞上,只有在體內(nèi)炎癥的病理?xiàng)l件下,才表達(dá)于活化的血管內(nèi)皮上;而后者除了表達(dá)在白細(xì)胞表面,還可以表達(dá)在子宮內(nèi)膜上皮、間質(zhì)細(xì)胞、血管內(nèi)皮細(xì)胞。因此,我們推測VCAM-1和ICAM-1可能參與了子宮內(nèi)膜異位癥的發(fā)生發(fā)展過程,對(duì)異位內(nèi)膜的種植、粘附、增殖發(fā)揮著重要作用。研究目的:通過檢測VCAM-1和ICAM-1在子官內(nèi)膜異位癥(EMs)患者異位內(nèi)膜、在位內(nèi)膜、非EMs患者子宮內(nèi)膜組織和血清中的表達(dá),探討VCAM-1和ICAM-1在子宮內(nèi)膜異位發(fā)病過程中的作用及臨床意義。材料與方法:收集我院盆腔子宮內(nèi)膜異位癥Ⅲ、Ⅳ期(根據(jù)r-AFs分期)患者的卵巢異位囊腫壁上的異位子宮內(nèi)膜作為異位內(nèi)膜組,其中行宮腔鏡檢查的子宮內(nèi)膜作為對(duì)應(yīng)的在位內(nèi)膜組,選擇同期因原發(fā)不孕、繼發(fā)不孕癥(輸卵管因素,排除內(nèi)異癥)行宮-腹腔鏡檢查的患者,取其子宮內(nèi)膜作為對(duì)照正常子宮內(nèi)膜組。此外,選擇腹腔鏡手術(shù)并確診的盆腔子宮內(nèi)膜異位癥患者術(shù)前血清作為血清病例組,選擇同期因不孕癥(輸卵管因素,排除內(nèi)異癥)患者行腹腔鏡手術(shù)的術(shù)前血清作為血清對(duì)照組。通過Real-time PCR檢測VCAM-1mRNA及ICAM-1 mRNA在不同子宮內(nèi)膜的表達(dá);通過Western blot方法檢測對(duì)VCAM-1及ICAM-1蛋白在不同子宮內(nèi)膜中的表達(dá)并進(jìn)行半定量分析;通過ELISA技術(shù)檢測內(nèi)異癥患者及對(duì)照組血清中sVCAM-1及sICAM-1吸光度(OD值)并進(jìn)行濃度計(jì)算。結(jié)果:1.Real-time PCR結(jié)果:VCAM-1mRNA在異位子宮內(nèi)膜組與在位內(nèi)膜組、對(duì)照組之間比較均有顯著性差異,具有統(tǒng)計(jì)學(xué)意義(P0.01,P0.01)。而在位內(nèi)膜組與對(duì)照組比較無統(tǒng)計(jì)學(xué)意義(P0.05)。ICAM-1mRNA在異位子宮內(nèi)膜組分別與在位內(nèi)膜組、對(duì)照組比較有顯著性差異,具有統(tǒng)計(jì)學(xué)意義(P0.01,P0.01),而在位子宮內(nèi)膜組與對(duì)照組比較無統(tǒng)計(jì)學(xué)意義(P0.05)。2.Western blot結(jié)果:VCAM-1在異位子宮內(nèi)膜組、在位內(nèi)膜組及對(duì)照組之間兩兩比較均有顯著性差異,具有統(tǒng)計(jì)學(xué)意義(P0.01),表達(dá)的強(qiáng)弱順序?yàn)?異位內(nèi)膜組在位內(nèi)膜組對(duì)照組。ICAM-1在異位子宮內(nèi)膜組分別與在位內(nèi)膜組、對(duì)照組比較有顯著性差異,具有統(tǒng)計(jì)學(xué)意義(P0.01,P0.01),而在位子宮內(nèi)膜組與對(duì)照組比較ICAM-1的相對(duì)表達(dá)量無統(tǒng)計(jì)學(xué)意義(P0.05)。3.ELISA結(jié)果:根據(jù)OD值和標(biāo)準(zhǔn)曲線計(jì)算EMs患者血清中的sVCAM-1及sICAM-1平均濃度與對(duì)照組比較均明顯升高,差異具有統(tǒng)計(jì)學(xué)意義(P0.01,P0.01)。sICAM-1濃度在Ⅲ、Ⅳ期組比Ⅰ、Ⅱ期組明顯升高,差異具有統(tǒng)計(jì)學(xué)意義(P0.01)。sVCAM-1在早期Ⅰ、Ⅱ期患者的血清濃度高于對(duì)照組(P0.01),差異具有統(tǒng)計(jì)學(xué)意義。采用ROC曲線分析,血清中sICAM-1和sVCAM-1在診斷子宮內(nèi)膜異位癥患者中具有一定的準(zhǔn)確性。其中,sICAM-1具有較高的特異性,敏感性偏低。結(jié)論:1.VCAM-1和ICAM-1通過在子宮內(nèi)膜異位癥患者中的mRNA水平、組織蛋白水平及血清中的高表達(dá)可能參與了子宮內(nèi)膜異位癥的發(fā)生、發(fā)展,在發(fā)病機(jī)制中具有重要作用。2.VCAM-1和ICAM-1在子宮內(nèi)膜異位癥患者的異位內(nèi)膜和在位內(nèi)膜組織蛋白中的表達(dá)無明顯相關(guān)性,提示兩者在子宮內(nèi)膜異位癥的致病機(jī)制可能是不同的。3.外周血sICAM-1和sVCAM-1在診斷子宮內(nèi)膜異位癥患者中具有一定的準(zhǔn)確性。檢測血清sICMA-1的濃度可以了解內(nèi)異癥的進(jìn)展?fàn)顩r,可能成為診斷內(nèi)異癥的新方法。
[Abstract]:Background: the incidence of endometriosis (endometriosis, EMs) in women of childbearing age is up to 10% to 15%. In recent years, the incidence of endometriosis is rising. It refers to the growth of endometriosis with endometriosis to the endometrium and the tissues outside the intrauterine layer, often with chronic pelvic pain, dysmenorrhea, and infertility. The pathogenesis of endometriosis is still not completely clear at present. Endometriosis is a benign disease, but it has great similarity with malignant tumor in many aspects, such as invasion, angiogenesis, proliferation, apoptosis and so on. Existing studies have found the immune cells in the abdominal environment of EMs patients, the changes of cytokines, and think that the immune mechanism is abnormal in EM The occurrence of s plays an important role in the process of development. There are many cell adhesion molecules (cell adhesion molecules, CAMs) expression in the endometrium epithelium and basement membrane. More and more studies have shown that abnormal expression of certain CAMs may be involved in the invasion, adhesion and planting process of EMs. The adhesion molecules of vascular cells (vascular cell adhesi) On molecule 1, VCAM-1) and intercellular adhesion molecules (intercellular adhesion molecule 1, ICAM-1) are two important members of the immunoglobulin superfamily, all of which are transmembrane glycoprotein adhesion molecules. The former is mainly distributed on activated endothelial cells, dendritic cells, only under the pathological conditions of inflammation in the body to be expressed in activation. In addition to the expression on the white cell surface, the latter can also be expressed in the endometrium epithelium, interstitial cells and vascular endothelial cells. Therefore, we speculate that VCAM-1 and ICAM-1 may be involved in the development and development of endometriosis, and play an important role in the planting, adhesion and proliferation of ectopic endometrium. To detect the expression of VCAM-1 and ICAM-1 in endometriosis (EMs) patients with endometriosis (EMs), eutopic endometrium, the expression of endometrium and serum in non EMs patients, and explore the role and clinical significance of VCAM-1 and ICAM-1 in endometriosis process. Materials and methods: collection of pelvic endometriosis in our hospital, stage III, IV (according to r-AFs staging). The ectopic endometrium on the wall of the ectopic cyst of the ovary of the patient is the ectopic endometrium group, and the endometrium of the hysteroscopy is used as the corresponding eutopic endometrium, and the endometrium of the patients with primary infertility, secondary infertility (fallopian tube factors, excluding the endometriosis) and the endometrium as the normal uterus are chosen at the same time. In addition, the preoperative serum of patients with pelvic endometriosis diagnosed by laparoscopy was selected as a serum case group, and the preoperative serum of patients with infertility (fallopian tube factors excluding endometriosis) underwent laparoscopic surgery as a serum control group. Real-time PCR was used to detect VCAM-1mRNA and ICAM-1 mRNA in different uterus. The expression of the endometrium and the expression of VCAM-1 and ICAM-1 protein in different endometrium by Western blot method and semi quantitative analysis; sVCAM-1 and sICAM-1 absorbance (o value) in serum of patients with endometriosis and control group were measured and calculated by ELISA technique. Fruit: 1.Real-time PCR result: VCAM-1mRNA in ectopic uterus Compared with the control group, there were significant differences between the control group and the control group (P0.01, P0.01), but there was no statistical significance (P0.05) between the eutopic and control group (P0.05).ICAM-1mRNA in the ectopic endometrium group and the eutopic endometrium group respectively, the control group had significant difference (P0.01, P0.01), but in the control group, there was a statistically significant difference between the control group and the control group. There was no significant difference (P0.05).2.Western blot results in the endometrium group with the control group (P0.05): VCAM-1 was significantly different in the ectopic endometrium group, in the eutopic endometrium group and the control group, with statistical significance (P0.01). The order of the expression was as follows: the eutopic endometrium group control group.ICAM-1 was in the ectopic uterus. There was significant difference between the control group and the control group, and the control group was statistically significant (P0.01, P0.01), while the relative expression of ICAM-1 in the eutopic endometrium group and the control group was not statistically significant (P0.05).3.ELISA results: the average concentration of sVCAM-1 and sICAM-1 in the serum of EMs patients was calculated according to the OD value and the standard curve, and the control was compared with the control group. The difference was significantly higher, the difference was statistically significant (P0.01, P0.01).SICAM-1 concentration in stage III, stage I and stage II, the difference was significant (P0.01), the difference was statistically significant (P0.01) in the early stage I, the serum concentration of stage II patients was higher than that of the control group (P0.01), the difference was statistically significant. The ROC curve analysis, serum sICAM-1 and s were used. VCAM-1 has a certain accuracy in the diagnosis of endometriosis. Among them, sICAM-1 has high specificity and low sensitivity. Conclusion: 1.VCAM-1 and ICAM-1 can participate in the occurrence and development of endometriosis through the level of mRNA in patients with endometriosis. There is no significant correlation between the expression of.2.VCAM-1 and ICAM-1 in the endometriosis of the patients with endometriosis and the expression of the eutopic tissue protein in endometriosis, suggesting that the pathogenesis of endometriosis may be the different.3. peripheral blood sICAM-1 and sVCAM-1 in the diagnosis of endometriosis patients. There is a certain degree of accuracy. Detection of serum sICMA-1 concentration can help to understand the progress of endometriosis and may become a new diagnostic method for endometriosis.

【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R711.71

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