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孕酮水平對(duì)小鼠子宮內(nèi)膜蛻膜化的影響及其形態(tài)計(jì)算機(jī)三維重組

發(fā)布時(shí)間:2018-08-17 17:23
【摘要】: 子宮是親代與后代個(gè)體之間生命延續(xù)的器官,作為一個(gè)生命孕育和最初生長的器官有著它一定的特性,例如月經(jīng)的發(fā)生、與受精卵生長相適應(yīng)的一系列變化等。子宮內(nèi)膜的周期性變化主要由于垂體-卵巢軸的激素變化產(chǎn)生。隨著卵泡的成熟、排卵,體內(nèi)的雌、孕激素也發(fā)生著周期性的波動(dòng),雌、孕激素周期性的波動(dòng)是月經(jīng)現(xiàn)象產(chǎn)生的直接原因。 由此可以看出,子宮是激素敏感器官,因此激素的不穩(wěn)定就會(huì)使子宮產(chǎn)生異常的變化。在臨床上,子宮內(nèi)膜的異常出血是困擾婦產(chǎn)科臨床和計(jì)劃生育實(shí)踐的重要臨床現(xiàn)象。子宮內(nèi)膜的異常出血是相對(duì)于正常的周期性出血而言的,因此,闡明一般周期性出血的成因?qū)ρ芯孔訉m內(nèi)膜異常出血也具有一定意義。 孕酮是雌性動(dòng)物體內(nèi)非常重要的性腺類固醇激素。既往的研究指出,孕酮是導(dǎo)致子宮周期性出血的重要因素。在整個(gè)月經(jīng)周期中,多種激素發(fā)生波動(dòng),但孕酮的下降是導(dǎo)致子宮內(nèi)膜蛻膜組織壞死崩解并出血的關(guān)鍵因素。既往實(shí)驗(yàn)實(shí)驗(yàn)主要是在模擬月經(jīng)周期的激素水平波動(dòng),在實(shí)驗(yàn)的最終都會(huì)發(fā)生孕酮的撤退。但根據(jù)臨床報(bào)告,大多數(shù)不規(guī)律出血的患者其體內(nèi)孕酮水平并沒有降低到月經(jīng)周期分泌晚期的撤退水平,因此我們嘗試在孕酮維持的狀態(tài)下觀察小鼠子宮內(nèi)膜蛻膜的變化,這對(duì)于進(jìn)一步闡明孕酮對(duì)于出血的影響有重要的意義。 本實(shí)驗(yàn)用孕酮皮埋管維持小鼠體內(nèi)的孕酮水平。首先確定皮埋管長度與所維持小鼠體內(nèi)孕酮水平之間的關(guān)系。經(jīng)測定,1cm長孕酮皮埋管所維持激素水平與小鼠妊娠第5天體內(nèi)激素水平相當(dāng)。所維持孕酮水平隨皮埋管有效長度增長而升高,且存在較好的線性關(guān)系。這為我們后期就孕酮維持小鼠模型的建立做好準(zhǔn)備。 在小鼠月經(jīng)模型的基礎(chǔ)上,建立小鼠人工誘導(dǎo)蛻膜化孕酮水平維持模型。此模型與文獻(xiàn)報(bào)告的三個(gè)模型的區(qū)別在于在小鼠蛻膜化模型的基礎(chǔ)上維持孕酮水平,繼而觀察蛻膜的變化。我們根據(jù)文獻(xiàn)所報(bào)告的方法,通過調(diào)節(jié)皮埋管長度使小鼠體內(nèi)孕酮水平在實(shí)驗(yàn)觀察階段恒定于某一水平并連續(xù)監(jiān)測陰道出血,觀察孕酮水平與出血、出血時(shí)間的關(guān)系以及崩解后小鼠子宮內(nèi)膜蛻膜組織的變化。結(jié)果提示,連續(xù)觀察的120-248小時(shí)過程中,小鼠子宮內(nèi)膜在維持孕酮的條件下仍然陸續(xù)發(fā)生了出血,組織切片顯示各組普遍出現(xiàn)了蛻膜壞死和崩解,出血時(shí)間隨孕酮水平的升高而延遲。 隨后我們觀察了當(dāng)孕酮水平維持在小鼠妊娠第5天水平下誘導(dǎo)蛻膜化后,不同時(shí)間的變化。我們分別觀察了誘導(dǎo)蛻膜化后96、120、144小時(shí)的變化。隨著觀察時(shí)間的延長,組織壞死程度逐漸加深。在誘導(dǎo)后96小時(shí),大體觀察組織可看到蛻膜化區(qū)域呈結(jié)節(jié)樣。切片觀察可發(fā)現(xiàn)在宮腔中央有一空泡,蛻膜化組織中充滿大量擴(kuò)張血管。在誘導(dǎo)后144小時(shí),壞死組織滯留于宮腔中且宮腔上皮未發(fā)生修復(fù)。實(shí)驗(yàn)中沒有胚胎,僅通過宮腔注油給予宮腔上皮著床刺激,所觀察到的變化為單純的母體的變化。這些變化與妊娠子宮部分結(jié)構(gòu)和變化相似。提示在妊娠過程中的一些變化與胚胎無關(guān)。 在孕酮水平維持的過程中我們發(fā)現(xiàn)如果孕酮水平維持且蛻膜組織沒有崩解時(shí),子宮內(nèi)膜中就會(huì)出現(xiàn)一些特殊的組織形態(tài)。在宮腔的中間會(huì)出現(xiàn)一個(gè)閉合的腔、閉合空腔周圍空腔,以及幾乎充滿整個(gè)子宮的血竇。我們想獲得這三種結(jié)構(gòu)的空間構(gòu)象。通過對(duì)組織連續(xù)切片并對(duì)其染色照相獲得了在每個(gè)斷層中三種結(jié)構(gòu)的形態(tài),后通過Adobe Photoshop以及Mimics軟件對(duì)切片圖像進(jìn)行處理并進(jìn)行三維重組,最終獲得了三種結(jié)構(gòu)空間構(gòu)型及其相互空間關(guān)系,這對(duì)于闡明血管及其他結(jié)構(gòu)在月經(jīng)及妊娠過程中的作用提供了有價(jià)值的信息,也對(duì)形態(tài)學(xué)研究提供了一種新手段。 本實(shí)驗(yàn)從組織形態(tài)學(xué)觀察到最后的方法學(xué)研究都有一定的創(chuàng)新性,并且得到較明確的結(jié)果。希望可以對(duì)子宮內(nèi)膜相關(guān)的研究提供有價(jià)值的信息。
[Abstract]:The uterus is the organ of life continuation between parent and offspring. As an organ of life gestation and initial growth, it has certain characteristics, such as the occurrence of menstruation, a series of changes adapted to the growth of fertilized eggs and so on. Maturity, ovulation, the body's estrogen, progesterone also occur periodic fluctuations, estrogen, progesterone periodic fluctuations are the direct cause of menstrual phenomena.
It can be seen from this that the uterus is a hormone sensitive organ, so the instability of hormones will cause abnormal changes in the uterus. Clinically, abnormal bleeding of the endometrium is an important clinical phenomenon in obstetrics and Gynecology and family planning practice. The cause of general periodic bleeding is also significant for studying abnormal bleeding of endometrium.
Progesterone is a very important gonadal steroid hormone in female animals. Previous studies have shown that progesterone is an important factor in causing periodic uterine bleeding. During the whole menstrual cycle, a variety of hormones fluctuate, but the decrease of progesterone is a key factor in causing endometrial and decidual tissue necrosis, disintegration and bleeding. But according to clinical reports, progesterone levels in most patients with irregular bleeding did not decrease to the level of withdrawal at the end of the menstrual cycle, so we tried to observe the endometrium of mice with progesterone maintenance. The change of decidua is important for further clarifying the effect of progesterone on bleeding.
The progesterone level in mice was maintained by a progesterone tube. First, the relationship between the length of the tube and the progesterone level in mice was determined. And there is a good linear relationship. This will prepare us for the establishment of progesterone maintenance mouse model in the later stage.
Based on the menstrual model of mice, a model of progesterone maintenance induced by artificial decidualization was established. The difference between this model and the three models reported in the literature was that progesterone levels were maintained on the basis of the mouse model of decidualization, and then the changes of decidua were observed. The progesterone level in mice was constant at a certain level during the experimental observation period and the vaginal bleeding was continuously monitored to observe the relationship between progesterone level and bleeding, bleeding time and the changes of endometrial Decidua Tissue after disintegration. Hemorrhage occurred successively. Tissue sections showed that decidual necrosis and disintegration were common in all groups. The time of bleeding was delayed with the increase of progesterone level.
Then we observed the changes of decidualization at different time points when progesterone levels were maintained at the 5th day of gestation in mice. We observed the changes at 96,120,144 hours after induction of decidualization. There was a vacuole in the center of the uterine cavity and a large number of dilated vessels were found in the decidualized tissue. At 144 hours after induction, the necrotic tissue was retained in the uterine cavity and the uterine epithelium was not repaired. Maternal changes. These changes are similar to some of the structures and changes of the pregnant uterus, suggesting that some changes during pregnancy are not related to the embryo.
During the maintenance of progesterone levels, we found that if progesterone levels were maintained and decidual tissue did not disintegrate, there would be some special histomorphology in the endometrium. In the middle of the uterine cavity there would be a closed cavity, a closed cavity around the cavity, and almost full of the uterine sinus. We wanted to obtain these three structures. Spatial conformation. Three kinds of structure shapes in each section were obtained by serial sections of tissue and staining photography. Then the slice images were processed and reconstructed by Adobe Photoshop and Mimics software. Finally, three kinds of structure spatial configuration and their spatial relationship were obtained. This is helpful to clarify the blood vessels and other knots. The role of structure in menstruation and pregnancy provides valuable information as well as a new means of morphological study.
We have observed from histomorphology that the final methodological study is innovative and has obtained definite results. We hope it can provide valuable information for endometrial-related research.
【學(xué)位授予單位】:中國協(xié)和醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2010
【分類號(hào)】:R339.2

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