大肠埃希菌致囊型肝包虫死亡的相关机制研究

A large number of clinical observation found that hepatic cystic echinococcosis(HCE) could die a in natural way, which could be triggered by bacterial infection and be manifested as liver abscess. HCE merged bacterial infections made hydatid cyst into abscess in a short time, and might induce rapid death. Combined with literature review, it was found that the main pathogenic bacteria of the bacterial infection of the liver were e. coli, and the most likely source was the intestinal bacteria being transferred by bile. However, there was no research on the mechanism of e. coli that caused the rapid death of the protoscoleces and the cysts. Therefore, this study intends to through the bile sources of E. Coli intervenes sheep sourced protoscoleces and young cysts, to observe the phenomenon of the death, and through the gross observation, pathology, molecular biology research, to explore the role of endoplasmic reticulum stress approach, mitochondria death way, oxidative stress reaction mechanism in this process. In addition, a model of bacterial infection was established to investigate the effects of e. coli on the lethal effect of echinococcus granulosus and to study the mechanism. To clarify this phenomenon and mechanism of this death way, which can provide more powerful evidence support for the decision-making of such patients in clinic, and provide a supplement to the natural course of the HCE.

大量临床观察发现，囊型肝包虫病可以发生自然死亡，其死亡的可能启动因素之一是合并细菌感染，造成类似肝脓肿的表现。肝包虫合并细菌感染可在短时间内使包虫囊肿脓肿化，并可能诱发快速死亡。结合文献复习发现，肝包虫细菌感染的主要病原菌是大肠杆菌，最可能的来源是肠道细菌经胆汁移位所致。但是大肠杆菌通过哪些机制导致细粒棘球蚴的原头蚴及幼囊的快速死亡，目前尚无研究。因此本研究拟通过使用胆汁来源的大肠杆菌干预羊源的细粒棘球蚴原头蚴及幼囊，观察原头蚴及幼囊的死亡现象，并通过大体观察、病理学、分子生物学等相关研究，探讨内质网应激反应、线粒体死亡途径、氧化应激反应等相关机制在此过程中的作用。此外，建立肝脏局部细粒棘球蚴以及细菌感染模型，进一步观察大肠杆菌对细粒棘球蚴的致死作用并探讨机制。细菌导致包虫死亡的现象及机制，可为临床上此类患者的决策提供更有力的证据支持，为肝包虫的自然病程的研究提供补充。

大量临床观察发现，囊型肝包虫病可以发生自然死亡，其死亡的可能启动因素之一是合并细菌感染，造成类似肝脓肿的表现。肝包虫合并细菌感染可在短时间内使包虫囊肿脓肿化，并可能诱发快速死亡。结合文献复习发现，肝包虫细菌感染的主要病原菌是大肠埃希菌，最可能的来源是肠道细菌经胆汁移位所致。但是大肠埃希菌通过哪些机制导致细粒棘球蚴的原头蚴及幼囊的快速死亡，目前尚无研究。本研究使用大肠埃希菌干预羊源的细粒棘球蚴原头蚴及幼囊，结果显示：感染不同浓度的大肠埃希菌对原头蚴和幼囊均有杀灭作用，感染大肠埃希菌浓度越高，作用时间越长，对细粒棘球蚴原头蚴和幼囊的生长活力影响效果越强并且大肠埃希菌可使原头蚴的生长环境变为酸性，进一步加强对细粒棘球蚴原头蚴和幼囊的杀灭作用；大肠埃希菌感染提高了GRP78蛋白表达水平，从而激活原头蚴内质网应激途径进促使虫体死亡；大肠埃希菌感染可提高了Bax表达降低了Bcl-2表达水平，并且随着菌液浓度升高和作用时间增加，使线粒体膜电位逐渐降低，表明线粒体死亡途径参与了大肠埃希菌致原头蚴的死亡过程；大肠埃希菌还可通过提高ROS的水平，上调Caspase-12、Capase-9、Capase-3蛋白的表达，促进细粒棘球蚴发生氧化应激从而导致细粒棘球蚴发生死亡。此上细菌导致包虫死亡的现象及机制，为临床上此类患者的决策提供了更有力的证据支持，为肝包虫的自然病程的研究提供了补充。