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陰道菌群移植對(duì)細(xì)菌性陰道感染疾病治療作用的初步研究

發(fā)布時(shí)間:2018-06-25 14:04

  本文選題:糞菌移植 + 陰道菌群; 參考:《南昌大學(xué)》2017年碩士論文


【摘要】:細(xì)菌性陰道病(Bacterial Vaginosis,BV)是一類由陰道微生態(tài)環(huán)境失調(diào)導(dǎo)致的婦科炎癥,常伴有盆腔炎、子宮內(nèi)膜炎和不孕不育等并發(fā)癥。作為陰道內(nèi)重要的功能菌群,乳酸菌在維持陰道內(nèi)環(huán)境穩(wěn)態(tài)的過(guò)程中發(fā)揮著重要作用,其數(shù)量下降會(huì)導(dǎo)致陰道pH值上升、酸性減弱,進(jìn)而造成陰道加德納菌、類桿菌等常見(jiàn)致病病原體大量增殖,造成不同程度的婦科炎癥。目前,抗生素仍是陰道婦科疾病的主要治療手段,但抗生素的濫用?蓪(dǎo)致宿主對(duì)抗生素的耐藥及對(duì)陰道正常功能菌群的破壞,致使陰道微生態(tài)環(huán)境進(jìn)一步失衡,婦科疾病易復(fù)發(fā)且不易根治的局面。鑒于糞菌移植技術(shù)在調(diào)節(jié)腸道菌群方面的良好效果,本研究團(tuán)隊(duì)首次提出陰道菌群移植的概念,即將健康宿主陰道分泌液中獲取的陰道菌群移植到患有細(xì)菌性陰道感染疾病的女性陰道中,達(dá)到重建患者陰道菌群微生態(tài)平衡,促進(jìn)其陰道內(nèi)環(huán)境的恢復(fù)、抑制致病菌的增殖,同時(shí)從根本上實(shí)現(xiàn)治療陰道婦科疾病的目的。本課題以細(xì)菌性陰道感染大鼠模型為研究對(duì)象,評(píng)價(jià)了陰道菌群移植技術(shù)對(duì)其的治療效果。研究結(jié)果表明,從健康大鼠收集到的陰道分泌物含總菌數(shù)約為105 CFU/mL,其中乳酸菌含量約為104 CFU/m L,占總菌數(shù)的7.8%。高通量測(cè)序結(jié)果表明,實(shí)驗(yàn)共得到622個(gè)OTUs,平均每組樣品含有103個(gè)OTUs;屬水平的聚類分析結(jié)果表明,陰道菌群主要由凝聚桿菌屬(Aggregatibacter)、擬桿菌屬(Bacteroides)、鏈桿菌屬(Streptobacillus)、梭菌屬(Fusobacterium)和卟啉單胞菌屬(Porphyromonas)構(gòu)成,其中優(yōu)勢(shì)凝聚桿菌屬(Aggregatibacter)在對(duì)照組(C組)占48.17%、模型組(M組)占59.37%、模型組治療期(M.M組)占27.06%、模型組恢復(fù)期(M.R組)占48.92%、治療組治療期(T.M組)占69.53%、治療組恢復(fù)期(T.R組)占53.97%;此外,Venn圖結(jié)果表明,菌群失調(diào)導(dǎo)致模型組陰道菌群多樣性降低,而陰道菌群移植后可將模型期中的102個(gè)OTUs上升至恢復(fù)期的172個(gè)OTUs,極大促進(jìn)了陰道菌群多樣性的恢復(fù)且增加了其微生物多樣性。HE結(jié)果表明,陰道菌群移植可極大緩解大鼠子宮組織出現(xiàn)的炎癥反應(yīng),降低內(nèi)膜充血和炎性細(xì)胞浸潤(rùn);從基因水平或蛋白水平顯著降低了大鼠促炎因子IL-1β、TNF-α和IL-6的含量(p0.01)。綜上所述,研究者首次提出陰道菌群移植治療陰道細(xì)菌感染疾病的理念,發(fā)現(xiàn)陰道菌群移植可顯著緩解陰道組織學(xué)病變,減緩其炎性因子釋放,并有助于陰道微生態(tài)動(dòng)態(tài)平衡的重建。本研究的開(kāi)展,為陰道菌群移植療法的深入研究提供了基礎(chǔ)數(shù)據(jù)和應(yīng)用依據(jù)。
[Abstract]:Bacterial Vaginosissis (BV) is a kind of gynecologic inflammation caused by the imbalance of vaginal microecological environment, often accompanied by pelvic inflammation, endometritis, infertility and other complications. As an important functional flora in the vagina, lactic acid bacteria play an important role in the process of maintaining the steady state of the vagina environment. The decrease in the number of lactic acid bacteria will lead to the increase of pH value and the weakening of the acidity of vagina, which will lead to Gardnebacterium vaginalis. A large number of pathogenic pathogens such as bacillus proliferate, resulting in different degrees of gynecological inflammation. At present, antibiotics are still the main treatment for gynecological diseases of vagina, but the abuse of antibiotics often leads to drug resistance of host to antibiotics and destruction of normal functional flora of vagina, resulting in further imbalance of microecological environment of vagina. Gynecological disease is easy to relapse and difficult to cure the situation. In view of the good effect of fecal bacteria transplantation in regulating intestinal flora, the concept of vaginal microflora transplantation was first put forward by the research team. The vaginal flora obtained from the vaginal secretions of healthy hosts was transplanted into the vagina of women with bacterial vagina infection, so as to reconstruct the microecological balance of the vaginal flora of the patients, promote the recovery of the vaginal environment and inhibit the proliferation of pathogenic bacteria. At the same time, the purpose of treating vaginal gynecological diseases is achieved. In this paper, the model of bacterial vagina infection in rats was studied to evaluate the therapeutic effect of vaginal microflora transplantation. The results showed that the total number of bacteria in vaginal secretions collected from healthy rats was about 105 CFU / mL, among which the content of lactic acid bacteria was about 104 CFU / mL, accounting for 7.8% of the total bacteria. The results of high-throughput sequencing showed that 622 OTUs were obtained, and 103 OTUs were found in each group of samples. The vaginal flora is mainly composed of (Aggregatibacter), Streptobacillus, Fusobacterium and Porphyromonas. Among them, 48.17% were dominant coagulans (group C), 59.37 were in model group (M group), 27.06g in model group (M.M group), 48.92% in model group (M.R group), 69.53 in treatment period (T.M group), and 69.53 in treatment group (T.R group), and 27.06% in model group (M.M group), 48.92% in model group (M.R group), 69.53% in treatment group (T.M group). 53.97; in addition, the Venn diagram shows that The diversity of vaginal flora in the model group was decreased due to the imbalance of the flora. However, after vaginal microflora transplantation, 102 OTUs in the model period were increased to 172 OTUs in the recovery period, which greatly promoted the recovery of vaginal flora diversity and increased the microbial diversity of vaginal flora. Vaginal microflora transplantation significantly alleviated the inflammatory reaction in rat uterus, reduced endometrial congestion and inflammatory cell infiltration, and significantly decreased the contents of IL-1 尾 -TNF- 偽 and IL-6 at gene level or protein level (p0.01). To sum up, the researchers first put forward the concept of vaginal microflora transplantation for the treatment of vaginal bacterial infection disease, and found that vaginal microflora transplantation can significantly alleviate the vagina histological lesions, slow down the release of inflammatory factors. It is helpful to reconstruct the dynamic balance of vagina microecology. The development of this study provides basic data and application basis for the further study of vaginal flora transplantation therapy.
【學(xué)位授予單位】:南昌大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R711.3

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