EHEC O157:H7感染严重威胁公共卫生和国家生物安全，其产生的志贺毒素（Stx2）损伤宿主肠粘膜上皮细胞，是导致出血性结肠炎等严重并发症甚至死亡的主要原因，其致病机制未揭示清楚。课题组前期观察到Stx2能诱导肠上皮细胞自噬型死亡（APCD），同时抑制内质网应激可减少自噬和细胞死亡，可能通过Akt/mTOR信号通路介导。本项目拟在体内外，通过上调或下调内质网应激和自噬，利用Western Blot、电镜、共聚焦等观察Stx2引起的肠上皮APCD及相关信号通路蛋白表达变化，并分析APCD与凋亡、坏死的关系，探讨"Stx2、内质网应激以及APCD"的作用模式，以期阐明内质网应激在Stx2毒素诱导肠上皮细胞自噬细胞死亡的机制,为EHEC O157:H7感染导致的疾病寻找新的防治手段提供理论依据。

EHEC O157:H7 infection is a serious threat to public health and national biosafety. Shiga toxin (Stx2) produced by this bacteria, which can damage the intestinal epithelial cells, is the main reason to cause hemorrhagic colitis and serious complications, but the pathogenic mechanisms did not reveal clear. In previous researches, our team observed that Stx2 can induce autophagic cell death (APCD) in intestinal epithelial cells, while inhibition of endoplasmic reticulum stress (ER stress) could decreased APCD,which may be mediated through Akt/mTOR signaling pathway. Through up or down regulating the expression of ER stress and autophagy in cell and animal models with Stx2 treatment,the present reserch tries to detect APCD and its signaling pathway with Western blot/electron microscopy/confocal laser microscope in intestinal epithelial cells, and analyze the relationship among the APCD/apoptosis/necrosis, to explore the model of "Stx2, ER stress and APCD". We intend to clarify the mechanism that ER stress regulates autophagic cell death induced by Stx2 in intestinal epithelial cells, and provide a theoretical basis for an effective treatment to EHEC O157:H7 infection.