本文選題：子宮移植 + 動(dòng)物實(shí)驗(yàn)　； 參考：《中國人民解放軍醫(yī)學(xué)院》2017年博士論文

【摘要】：研究背景：完全性子宮因素不孕(abso1ute uterine factor-inferti1ity AUFI)是女性不孕因素的一個(gè)主要類型,一直被認(rèn)為無法醫(yī)治,主要是因?yàn)檫@類女性先天性無子宮比如MRKH (Mayer-Rokitansky-Kuster-Hauser)綜合征患者或早期因?yàn)閷m頸癌、產(chǎn)科出血被迫切除子宮和因?yàn)閲?yán)重的子宮內(nèi)粘連導(dǎo)致沒有生育功能的育齡期女性,子宮移植(uterus transp1antation-UTx)的目的就是為先天或后天性因素導(dǎo)致子宮缺如或子宮畸形的育齡期女性移植一個(gè)有功能的子宮并生出一個(gè)孩子。人體子宮移植技術(shù)如果想要達(dá)到更安全的妊娠及活產(chǎn)仍需要大量的動(dòng)物實(shí)驗(yàn)研究來提供技術(shù)支持,在國內(nèi),異體子宮移植的大動(dòng)物實(shí)驗(yàn)研究一直處于探索階段,鮮有相關(guān)研究報(bào)道;另外,在臨床領(lǐng)域,育齡期子宮因素不孕女性對(duì)UTx的態(tài)度與意愿是不知的。研究目的:1.探討小型豬異體子宮移植活體捐贈(zèng)技術(shù)的可行性和安全性,觀察子宮移植后動(dòng)物的長期存活及生殖功能恢復(fù);2.探討稱猴異體子宮移植活體捐贈(zèng)的手術(shù)技巧,評(píng)估獼猴子宮肌層組織耐受冷缺血損傷的時(shí)限;3.調(diào)查MRKH綜合征患者對(duì)子宮移植的態(tài)度和意愿,為下一步人體子宮移植提供臨床數(shù)據(jù)和志愿者。方法:1.選用10頭雌性、月經(jīng)規(guī)律的小型豬,根據(jù)一母同源(同胞生)和體重匹配5頭作為供體,5頭作為受體(n=5),從活體供體盆腔獲取子宮及主要血管,使用4℃C器官保存液對(duì)離體器官冷保存、灌注,之后將供體子宮原位移植到受體盆腔,移植的髂內(nèi)動(dòng)脈與受體髂外動(dòng)脈端-側(cè)吻合;2.術(shù)后5例受體均給予三聯(lián)免疫抑制劑維持治療,術(shù)后1周和1個(gè)月行多普勒超聲觀察移植子宮的動(dòng)脈血流信號(hào)及盆腔情況,術(shù)后2個(gè)月全麻下行二次開腹觀察移植子宮及盆腔情況,術(shù)后刺激發(fā)情期并對(duì)對(duì)明顯有發(fā)情期的動(dòng)物進(jìn)行人工胚胎移植;3.選用性成熟、月經(jīng)規(guī)律的雌性獼猴2只,根據(jù)血型和體重選取供體1例和受體1例(n=1),將切除的供體子宮原位移植到受體盆腔,術(shù)后1個(gè)月復(fù)查超聲觀察移植子宮情況;并將切除的受體子宮在冷保存前快速取部分宮角組織作為對(duì)照組,剩余組織使用4℃CUW (university of wisconsin)器官保存液中冷保存4h和8 h作為實(shí)驗(yàn)組,固定后的標(biāo)本使用電鏡及光鏡觀察子宮肌層組織不同冷缺血保存時(shí)限的病理改變;4.收集2005年12月-2015年12月在解放軍總醫(yī)院、武警總醫(yī)院因先天性無子宮、無陰道行陰道成形術(shù)住院治療的育齡期MRKH(mayer-rokitansky-kuster-hauser)綜合征患者共31例,多次電話隨訪這類患者實(shí)施子宮移植的態(tài)度和意愿,調(diào)查MRKH綜合征患者對(duì)子宮移植、收養(yǎng)、代孕的看法和選擇。結(jié)果:1.5例小型豬異體子宮移植中無1例出現(xiàn)術(shù)中、術(shù)后并發(fā)癥,髂血管吻合后均可觸及血管搏動(dòng),5例受體中4例存活3個(gè)月以上,術(shù)后經(jīng)腹超聲于移植子宮旁及髂血管旁均可見動(dòng)脈血流信號(hào),UTx5術(shù)后第3天死亡,死亡原因?yàn)榧毙耘懦饣蚋腥疽鸬淖訉m壞死,總的子宮移植成功率100%,受體長期存活率80%, UTx2術(shù)后3個(gè)月出現(xiàn)發(fā)情期并行人工胚胎移植,21天后行超聲未發(fā)現(xiàn)妊娠;2.1例獼猴異體子宮移植術(shù)中髂血管吻合成功,術(shù)后動(dòng)物存活28天,死亡原因?yàn)槁运ソ�。與對(duì)照組相比,獼猴子宮肌層組織在電鏡下,使用4℃CUW器官保存液冷保存4h后未見明顯改變,冷保存8h后發(fā)現(xiàn)核膜腫脹,核分裂,線粒體腫脹;光鏡下,冷保存4h和8h后的子宮肌組織均未發(fā)現(xiàn)明顯改變;3.31例育齡期MRKH綜合征患者,有子宮移植意愿:6例,19.3%,有意愿但需要考慮或討論的:18例,58%,無子宮移植意愿:4例,12.9%,沒有表達(dá)觀點(diǎn):3例,9.6%; 18例需要考慮或討論的問題:經(jīng)濟(jì)6例,33.3%、自己和供體可能存在的手術(shù)風(fēng)險(xiǎn)5例,27.7%、術(shù)后免疫抑制劑的副作用3例,16.6%,需要家人的支持4例,22.2%,在選擇擁有孩子的方式中:子宮移植8人,25.8%,代孕 6 人,19.3%,收養(yǎng) 12 人,38.7%,其他 5 人,16.1%。結(jié)論:1.小型豬作為異體子宮移植活體捐贈(zèng)手術(shù)是可行的,僅使用動(dòng)脈系統(tǒng)作為移植血管受體能夠長期存活且能夠恢復(fù)發(fā)情期,術(shù)后超聲監(jiān)測(cè)能較好的評(píng)估移植子宮動(dòng)脈血流;2.獼猴的是進(jìn)行異體子宮移植最合適的動(dòng)物模型,且子宮肌層組織至少能夠耐受UW器官保存液冷保存4小時(shí);3.育齡期MRKH綜合征患者與代孕相比更愿意選擇子宮移植技術(shù)來擁有一個(gè)孩子。
[Abstract]:Background: complete uterine factor infertility (abso1ute uterine factor-inferti1ity AUFI) is a major type of female infertility, which has been considered untreatable, mainly because of this type of female congenital absence of uterus such as MRKH (Mayer-Rokitansky-Kuster-Hauser) syndrome or early due to cervical cancer, obstetric hemorrhage Women of childbearing age who are forced to remove the uterus and cause no reproductive function because of severe intrauterine adhesions. The purpose of uterus transp1antation-UTx is to transplant a functional uterus and produce a child for a female with congenital or acquired factors that cause uterine deformity or uterine malformation. In order to achieve safer pregnancies and live births, a large number of animal experiments are needed to provide technical support. At home, large animal experimental studies of allogeneic uterine transplants have been at the exploratory stage, and there are few related reports. In addition, in the clinical field, the attitude and willingness of women with childbearing age subuterine factors to UTx are not known. Objective: 1. to explore the feasibility and safety of living donor donation technique for small pig uterus allograft, observe the long-term survival and reproductive function recovery of the animals after the uterus transplantation; 2. explore the surgical techniques for the living donor donation of the monkey allograft, evaluate the time limit for the cold ischemia injury in the macaque myometrium group, and 3. investigate the MRKH synthesis The patient's attitude and willingness to transplant the uterus to provide clinical data and volunteers for the next step of human uterine transplantation. 1. small pigs with 10 female and menstrual regularities were used as donors and 5 heads (n=5) based on a parent homologous (SIB) and body weight as a donor (n=5). The uterus and the main blood vessels were obtained from the pelvic cavity of the living body, using 4 centigrade C The organ preservation solution was cryopreserved and perfused to the isolated organs, then the donor uterus was transplanted in situ to the recipient pelvic cavity, and the transplanted iliac artery was anastomosed with the recipient external iliac artery end to side. 2. after the operation, 5 cases were treated with triple immunosuppressive agents, and the arterial blood flow signals and pelvic cavity were observed by Doppler ultrasound at 1 and 1 months after the operation. 2 months after the operation, the uterus and the pelvic cavity were observed two times under general anesthesia. After the operation, the oestrus was stimulated and the artificial embryos were transplanted to the apparently estrous animals. 3. female rhesus monkeys with sexual maturity and menstruation were selected to select the donor 1 cases and 1 recipients (n=1) according to the blood type and body weight, and the original displacement of the donor uterus was removed. The transplanting uterus was observed after 1 months after 1 months, and the uterus of the resected receptor uterus was taken as the control group quickly before the cold preservation. The remaining tissues were treated as the experimental group with cold preservation 4H and 8 h in the 4 CUW (University of Wisconsin) organ preservation solution. The specimens after the fixation were used by electron microscopy and light microscopy. Observe the pathological changes of different cold ischemic preservation time limits in the uterine myometrium; 4. collect 31 cases of childbearing age MRKH (Mayer-Rokitansky-Kuster-Hauser) syndrome in the General Hospital of PLA in December 2005 -2015, at the General Hospital of the PLA, because of congenital no uterus and vaginal vaginoplasty. The attitudes and wishes of the uterus transplantation were carried out to investigate the views and choices of MRKH syndrome patients for uterine transplantation, adoption, and surrogate. Results: there were no 1 cases in 1.5 cases of miniature pig allograft, postoperative complications, vascular pulsation after iliac vascular anastomosis, 4 cases in 5 patients survived more than 3 months, and postoperatively transabdominal ultrasound in transplantation The arterial blood flow signals were observed at the paranoal and iliac vessels. UTx5 died third days after the operation. The cause of death was acute rejection or infection induced uterine necrosis. The total success rate of the uterus was 100%, the long-term survival rate of the receptor was 80%. The oestrus parallel artificial embryo transfer was found at 3 months after the operation, and the pregnancy was not detected by ultrasound in 21 days; 2.1 cases of macaque allograft were not found. The iliac vascular anastomosis was successful during the operation of the uterus transplantation. The postoperative animal survived 28 days and the cause of death was chronic failure. Compared with the control group, the myometrium of the macaque was not significantly changed after the cryopreservation of 4H under the electron microscope. After the cold preservation of 8h, the swelling of the nuclear membrane, the mitosis, the swelling of mitochondria, and the cold preservation of 4H and 8h after the cold preservation were found. No significant changes were found in the myometrium of the uterus; 3.31 cases of MRKH syndrome in the childbearing age had the intention of transplanting uterus: 6 cases, 19.3%, willing but need to be considered or discussed: 18 cases, 58%, no uterine transplant Willingness: 4 cases, 12.9%, no expression of Views: 3 cases, 9.6%; 18 cases need to be considered or discussed: the economy 6, 33.3%, oneself, and donor may deposit 5 cases of operation risk, 27.7%, side effects of immunosuppressants after operation, 3 cases, 16.6%, 4 cases of family support, 22.2% in the choice of children with 8, 25.8%, 6, 19.3%, 12, 38.7%, and other 5, 16.1%. conclusion: it is feasible to operate as a living donor for allogeneic uterine transplantation. The use of the arterial system as a transplant recipient can survive for a long time and can restore the oestrus. The postoperative ultrasound monitoring can better evaluate the blood flow of the transplanted uterine artery; 2. the macaque is the most suitable animal model for the allograft of the uterus, and the myometrium of the uterus can tolerate at least 4 hours of UW organ preservation and 4 hours; 3. of the childbearing age. The combined patients are more willing to choose uterine transplant technology to have one child than surrogacy.
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R-332;R711.6

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相關(guān)期刊論文 前1條

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本文編號(hào)：1911640