大肠杆菌诱导人巨噬细胞系U937细胞凋亡及其机制的研究

发布时间：2018-07-31 13:16

【摘要】：前言在抗感染药物广泛使用的时代,感染性疾病仍然是人类健康的重要威胁。随着抗感染药物的广泛应用,常见病原体对于常用抗感染药物逐渐出现耐药性,而且耐药性发生迅速。因此,从事与抗感染治疗相关的人员不得不重新思考抗感染策略,那就是从感染性疾病的发病机制上来重新认识感染性疾病,以期发现新的抗感染途径。细胞凋亡是在基因调控下进行的主动、有序的死亡过程,在正常生长发育和新陈代谢过程中对于清除不必要的细胞起到非常重要的作用。现已发现许多病原体能够诱导宿主细胞凋亡,因此可以影响疾病的进程。大肠杆菌(Escherichia coli,E.coli)是自然界普遍存在的条件致病菌。在正常情况下感染E.coli一般不致病,是人体不可缺少的有益菌,但当它侵入盲肠、胆囊、腹腔、泌尿系统时,则可引起炎症反应。有时新生儿和2岁以内婴幼儿的腹泻和胃肠炎是由致病性E.coli引起的,有些菌株还可以引起细菌性食物中毒。巨噬细胞是机体重要的防御细胞,若巨噬细胞凋亡增加,将严重影响其功能的发挥,使其吞噬处理能力下降。很多研究中,都把U937细胞作为单核/巨噬细胞的实验模型。探讨E.coli感染与U937细胞凋亡的关系,将有助于从分子水平上更好地阐明E.coli的致病机制,为开发新型抗感染药物提供重要的理论根据。许多研究证明了在不同的疾病和生理性细胞死亡过程中参与细胞死亡信号途径的许多因素。Bcl-2及其家族的其他成员在胚胎形成、组织修复和免疫反应过程中作为抑制或促进凋亡的因素起到非常重要的作用。Bcl-2通常具有抗凋亡的作用,Bax是Bcl-2家族的一个成员,通常促进细胞凋亡。以往的研究证明了Bcl-2和Bax在细胞凋亡过程中所起的作用。然而,Bcl-2和Bax是否参与了E.coli诱导人巨噬细胞系U937细胞凋亡的过程目前尚不清楚。
[Abstract]:In the era of widespread use of anti-infective drugs, infectious diseases are still an important threat to human health. With the wide application of anti-infective drugs, common pathogens gradually develop resistance to common anti-infective drugs, and drug resistance occurs rapidly. Therefore, people involved in anti-infection therapy have to rethink the anti-infection strategy, that is, to re-understand infectious diseases from the pathogenesis of infectious diseases, in order to find new anti-infective pathways. Apoptosis is an active and orderly process of death under the regulation of genes, which plays a very important role in eliminating unnecessary cells during normal growth, development and metabolism. Many pathogens have been found to induce apoptosis in host cells, thus affecting disease progression. Escherichia coli (E. coli) is a common conditional pathogen in nature. Infection with E.coli is generally non-pathogenic and is an indispensable and beneficial bacterium, but when it invades the caecum, gallbladder, abdominal cavity and urinary system, it can cause inflammation. Sometimes diarrhea and gastroenteritis in newborns and children under 2 years of age are caused by pathogenic E.coli, and some strains can cause bacterial food poisoning. Macrophages are important defensive cells in the body. If the apoptosis of macrophages increases, the function of macrophages will be seriously affected and the phagocytosis ability will be decreased. In many studies, U937 cells were used as experimental models of mononuclear / macrophages. To explore the relationship between E.coli infection and U937 cell apoptosis will be helpful to better elucidate the pathogenesis of E.coli at molecular level and provide an important theoretical basis for the development of new anti-infective drugs. Many studies have shown that many of the factors involved in the signaling pathway of cell death in different diseases and physiological cell death pathways. Bcl-2 and other members of their families are involved in embryogenesis. Bax is a member of Bcl-2 family, which is a member of Bcl-2 family, and usually promotes cell apoptosis as a very important factor to inhibit or promote apoptosis in the process of tissue repair and immune response. Previous studies have demonstrated the role of Bcl-2 and Bax in the process of apoptosis. However, it is not clear whether Bcl-2 and Bax are involved in the apoptosis of human macrophage cell line U937 induced by E.coli.
【学位授予单位】：中国医科大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R378

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