产毒性大肠杆菌的致病机制

目的 深入分析产毒性大肠杆菌(ETEC)的致病机制。方法 建立ETEC感染豚鼠模型，采用免疫组织化学染色及流式细胞术，观察豚鼠肠组织的病理形态并测定细胞内游离Ca^2 、细胞质pH、细胞膜电位及线粒体膜电位。结果 豚鼠对人源ETEC菌株敏感，ETEC可导致豚鼠小肠充血、水肿和炎细胞浸润，未发现细菌人侵小肠上皮细胞，但电镜下可见小肠上皮细胞空泡样变性，线粒体增生；不耐热肠毒素(LT)和耐热肠毒素(ST)在回肠组织中分布弥漫；LT和ST均可使豚鼠小肠离体上皮细胞内游离Ca^2 、细胞浆pH和细胞跨膜电位上调，使线粒体跨膜电位下降。结论 ETEC可导致豚鼠小肠充血、水肿和炎细胞浸润等炎症反应；LT和ST的作用也不限于上皮细胞，对肌细胞也有影响；对肠毒素作用的分析提示，LT与ST的作用部位与机制可能相似，ETEC腹泻与细胞主动排水过程有关。

Pathogenic mechanisms of enterotoxigenic Escherichia coli in guinea pigs]

OBJECTIVE: To explore the pathogenic mechanisms of enterotoxigenic Escherichia coli (ETEC) in guinea pigs. METHODS: Pathological examination of the intestines was performed in ETEC-infected guinea pigs, and the intracellular free Ca2+ concentration, cytoplasmic pH, cell membrane potential and mitochondria membrane potential were determined immunohistochemically and by means of flow cytometry. RESULTS: The guinea pigs were sensitive to the human-origin ETEC, which caused pathological changes in the small intestines such as edema, hyperemia and lymphocyte infiltration, but no bacteria invasion into the epithelial cells was identified. Under transmission electron microscope, the ileal epithelial cells were shown with vacuolar degeneration and evidence of mitochondrial proliferation; heat-labile (LT) and heat-stable (ST) toxins pervaded in the ileal tissue, resulting in significant increase of intracellular free Ca2+ concentration, cytoplasmic pH value and cell membrane potential, with concomitance of significant decrease in mitochondrial membrane potential. CONCLUSIONS: ETEC disturbs the absorption and secretion functions of the intestinal epithelial cells, and induces extensive inflammation in the small intestines of guinea pigs. Besides their action on intestinal epithelial cells, LT and ST also affect the myocytes in the muscularis, and their action sites and mechanism might be similar. ETEC-induced diarrhea is correlated with excessive water excretion from the cells.