發(fā)布時(shí)間：2018-12-11 08:06

【摘要】：本實(shí)驗(yàn)通過復(fù)制化療損傷卵巢動(dòng)物模型,利用分離培養(yǎng)出的人羊膜間充質(zhì)干細(xì)胞(amniotic mesenchymalstem cells,AMSCs)與人臍帶間充質(zhì)干細(xì)胞(umbilical cord mesenchymal stem cells,UC-MSCs)進(jìn)行干預(yù),取對(duì)照組、模型組、AMSCs干預(yù)組、UC-MSCs干預(yù)組四組卵巢,以光學(xué)顯微鏡進(jìn)行組織形態(tài)學(xué)觀察、卵泡計(jì)數(shù)等相關(guān)分析。取各組大鼠不同時(shí)間點(diǎn)(干預(yù)后14天、30天、60天、90天)的血清測(cè)量E2、FSH、LH、VEGF、IGF-1的含量;取各組大鼠干預(yù)后30天、90天時(shí)的卵巢組織試樣,以電子萬能試驗(yàn)機(jī)進(jìn)行拉伸實(shí)驗(yàn)、應(yīng)力松弛實(shí)驗(yàn)、蠕變實(shí)驗(yàn)。對(duì)AMSCs干預(yù)組、UC-MSCs干預(yù)組大鼠干預(yù)結(jié)束后15d,按照雌雄比例2:1飼養(yǎng),均飼養(yǎng)6個(gè)月,觀察兩組大鼠生育能力的恢復(fù)情況,觀察生育的幼鼠生長(zhǎng)發(fā)育情況。結(jié)果表明,AMSCs干預(yù)組、UC-MSCs干預(yù)組血清中各時(shí)間點(diǎn)E2、VEGF、IGF-1測(cè)定值均大于化療損傷卵巢動(dòng)物模型組;FSH、LH測(cè)定值均小于模型組,差異顯著(p0.05)。AMSCs干預(yù)組、UC-MSCs干預(yù)組各時(shí)間點(diǎn)始基卵泡、竇前卵泡、竇狀卵泡及排卵前卵泡數(shù)均高于化療損傷卵巢動(dòng)物模型組,差異顯著(p0.05)。AMSCs干預(yù)組、UC-MSCs干預(yù)組拉伸最大應(yīng)力、最大應(yīng)變大于化療損傷卵巢動(dòng)物模型組,差異顯著(p0.05)。AMSCs干預(yù)組、UC-MSCs干預(yù)組大鼠血清中性激素水平、分子生物學(xué)指標(biāo)具有一定的恢復(fù),卵巢的組織形態(tài)、卵泡的數(shù)量、卵巢的彈性和韌性也得到一定的恢復(fù),并且部分大鼠恢復(fù)了生育能力。創(chuàng)新點(diǎn):以往對(duì)化療損傷卵巢動(dòng)物模型藥物干預(yù)治療效果的研究多以分子生物學(xué)、組織形態(tài)學(xué)觀察等進(jìn)行分析。本文除了從上述方面進(jìn)行分析研究,還加入了卵巢的拉伸力學(xué)特性、應(yīng)力松弛、蠕變特性等生物力學(xué)研究,進(jìn)一步探討化療損傷卵巢動(dòng)物模型以AMSCs、UC-MSCs干預(yù)治療的效果,為臨床提供了理論基礎(chǔ)和實(shí)驗(yàn)依據(jù)。
[Abstract]:In this experiment, the ovarian model was induced by chemotherapy, and the cultured human amniotic mesenchymal stem cells (amniotic mesenchymalstem cells,AMSCs) and human umbilical cord mesenchymal stem cells (umbilical cord mesenchymal stem cells,UC-MSCs) were used to intervene. AMSCs intervention group, UC-MSCs intervention group, four groups of ovary, optical microscope for histomorphological observation, follicle count and other related analysis. The serum of each group of rats at different time points (14 days, 30 days, 60 days, 90 days after the intervention) was taken to measure the content of E2FSHLHV EGFF-1; The ovarian tissue samples of each group were taken 30 days and 90 days after intervention, and the tensile test, stress relaxation test and creep test were carried out with the electronic universal testing machine. The rats in AMSCs intervention group and UC-MSCs intervention group were fed at 2:1 for 6 months according to the ratio of male and female at the end of the intervention. The recovery of fertility and the growth and development of the young rats in the two groups were observed. The results showed that the levels of E2VEGFIGF-1 in serum of AMSCs intervention group and UC-MSCs intervention group were higher than those of ovarian model group after chemotherapy. The number of primary follicles, preantral follicles, antral follicles and antral follicles in UC-MSCs intervention group were higher than those in the model group after chemotherapy. The difference was significant (p0. 05). AMSCs intervention group, UC-MSCs intervention group, the maximal tensile stress and maximum strain were higher than that of chemotherapy induced ovarian injury model group, the difference was significant (p0. 05). AMSCs intervention group, p0. 05). AMSCs intervention group). In UC-MSCs intervention group, the levels of serum sex hormones and molecular biological indexes recovered to a certain extent, and some of the rats recovered their fertility, such as the morphology of ovary, the number of follicles, the elasticity and toughness of ovary. Innovation: the previous studies on the therapeutic effect of drug intervention on ovarian model with chemotherapy injury were analyzed by molecular biology and histomorphology observation. In addition to the above aspects, the biomechanical studies on the tensile mechanical properties, stress relaxation and creep properties of the ovary were added to further explore the effect of AMSCs,UC-MSCs intervention in the treatment of the ovarian model with chemotherapy injury. It provides theoretical basis and experimental basis for clinical practice.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R711.75

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