本文選題：瘦素 + 瘦素受體��； 參考：《中國人民解放軍醫(yī)學(xué)院》2014年碩士論文

【摘要】：子宮內(nèi)膜異位癥（endometriosis, EMT）是一種具有惡性腫瘤生物學(xué)行為的婦科良性疾病，定義為細(xì)胞水平以上有活性的子宮內(nèi)膜組織（腺體和間質(zhì)）在子宮腔被覆內(nèi)膜及子宮肌層以外的部位出現(xiàn)、生長、浸潤、反復(fù)出血，可形成結(jié)節(jié)及包塊，引起疼痛、不育等。EMT的發(fā)病機制不清，研究表明瘦素及其受體的表達(dá)及調(diào)控在EMS發(fā)生發(fā)展過程中起重要作用，它參與了血管新生、細(xì)胞增殖與凋亡，免疫調(diào)節(jié)、炎癥反應(yīng)、新陳代謝。研究EMS病程中瘦素、瘦素受體及其上、下游因子的表達(dá)及變化規(guī)律，可為EMS發(fā)病機制的研究、臨床治療和新藥的開發(fā)應(yīng)用提供新的切入點。本研究共分為兩部分： 一、 SCID小鼠EMT異種移植模型的建立及因子的表達(dá) 探討leptin、OB-R及其上下游相關(guān)調(diào)控因子在SCID小鼠子宮內(nèi)膜移植病灶及小鼠子宮組織中的表達(dá)特點。建立子宮內(nèi)膜異位癥SCID小鼠異種皮下移植模型，，通過免疫組織化學(xué)法觀察各因子的表達(dá)。SCID小鼠異種皮下移植EMT模型成功率高，移植組織存活率高，觀察方便，實驗周期短，與人EMT的組織學(xué)與生化特征一致，可以從時間及空間上全面的反映EMT的病理生理特征。移植組織及小鼠子宮leptin、OB-R、STAT3及p-STAT3的表達(dá)強度及定位特征明確，可作為后續(xù)實驗的參照。 二、影響leptin、OB-R及STAT3表達(dá)的相關(guān)藥物對SCID小鼠子宮內(nèi)膜異位病灶的作用 應(yīng)用子宮內(nèi)膜異位癥的SCID小鼠模型，給予干預(yù)leptin代謝的相關(guān)藥物治療，觀察病灶及小鼠的變化情況，應(yīng)用實時熒光定量聚合酶鏈?zhǔn)椒磻?yīng)及免疫組織化學(xué)法，測定并定位相關(guān)因子的表達(dá)特征，分析并驗證所用藥物對子宮內(nèi)膜異位癥的治療作用及全身影響。結(jié)論如下：1.環(huán)磷酸腺苷可以抑制leptin的表達(dá)，但無法抑制下游OB-R、STAT3的表達(dá)及STAT3的活化，因而在EMT治療中所起的作用有限，具體機制有待進一步研究。2.左卡尼汀在急、慢性炎癥過程中，對leptin代謝的影響機制不同，不能降低EMT慢性炎癥過程中l(wèi)eptin、OB-R及STAT3的表達(dá)，不適用于對EMT的治療。3.米非司酮可以顯著降低leptin、OB-R及STAT3的表達(dá)，為治療EMT的有效藥物，但對體重有一定影響。4.孕激素對EMT病灶的抑制可能不通過leptin→OB-R→JAK2/STAT3途徑實現(xiàn)。5.S3I-201可以有效抑制EMT病灶中l(wèi)eptin、OB-R、STAT3的表達(dá)及STAT3的異常磷酸化，有望成為新的、有效的EMT治療藥物。 綜上所述，本研究表明： 1、leptin是EMT發(fā)生發(fā)展過程中的敏感指標(biāo)，可用于疾病診斷、療效判斷、復(fù)發(fā)檢測等，有望成為EMT參考監(jiān)測指標(biāo)。 2、對leptin和OB-R及其上、下游調(diào)控因子和相關(guān)信號通路的研究，有助于EMT發(fā)病機制的深入研究和藥物治療新靶點的開發(fā)。
[Abstract]:Endometriosis (EMTs) is a benign gynecological disease with the biological behavior of malignant tumor. Defined as the presence of active endometrial tissue (glands and stroma) above the cellular level in the area outside the endometrium and the myometrium of the uterine cavity, growing, infiltrating, bleeding repeatedly, forming nodules and masses, causing pain, The expression and regulation of leptin and its receptors play an important role in the development of EMS, which is involved in angiogenesis, cell proliferation and apoptosis, immune regulation, inflammatory response, metabolism. To study the expression and variation of leptin, leptin receptor and its upstream and downstream factors in the course of EMS may provide a new entry point for the study of the pathogenesis of EMS, the clinical treatment and the development and application of new drugs. This study was divided into two parts: first, the establishment of EMT xenotransplantation model and the expression of factors in SCID mice; the expression of leptinine OB-R and its upstream and downstream regulatory factors in SCID mouse endometrium transplantation focus and mouse uterus tissue. The xenotransplantation model of SCID mice with endometriosis was established. The expression of various factors in SCID mice was observed by immunohistochemical method. The success rate of xenotransplantation EMT model in SCID mice was high, the survival rate of transplanted tissue was high, the observation was convenient and the experimental period was short. The histopathological and biochemical characteristics of EMT are consistent with those of human EMT, which can reflect the pathophysiological characteristics of EMT in time and space. The expression intensity and localization of leptinine OB-RNT-STAT3 and p-STAT3 in transplanted tissues and mice uterus are clear and can be used as reference for further experiments. Effects of drugs related to the expression of leptinine OB-R and STAT3 on endometrial ectopic lesions in SCID mice models of endometriosis were used to observe the changes of lesions and mice. Real-time fluorescent quantitative polymerase chain reaction and immunohistochemical method were used to detect and locate the expression characteristics of related factors and to analyze and verify the therapeutic effect and systemic effect of the drugs on endometriosis. The conclusion is as follows: 1. Adenosine cyclophosphate can inhibit the expression of leptin, but it can not inhibit the expression and activation of STAT3 downstream. Therefore, the role of adenosine cyclophosphate in the treatment of leptin is limited, and the specific mechanism needs to be further studied. Levocarnitine does not decrease the expression of leptinine OB-R and STAT3 in the process of acute and chronic inflammation, and it is not suitable for the treatment of leptin. Mifepristone can significantly reduce the expression of leptinine OB-R and STAT3, which is an effective drug for the treatment of EMT, but has a certain effect on body weight. The inhibition of progesterone on EMT lesions may not be realized through the leptin OB-R jar 2 / STAT3 pathway. 5. S3I-201 can effectively inhibit the expression of leptinin OB-RtSTAT3 and abnormal phosphorylation of STAT3 in EMT lesions, which may be a new and effective therapeutic drug for EMT. The results show that: 1 leptin is a sensitive index in the course of occurrence and development of EMT, which can be used in disease diagnosis, curative effect judgment, recurrence detection and so on. 2. The study of leptin, OB-R and its upstream and downstream regulatory factors and related signal pathways. It is helpful for the further study of the pathogenesis of EMT and the development of new targets for drug therapy.
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R711.71

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本文編號：2004663