肠道疾病中肠上皮细胞的死亡
Saravanan Subramanian^1,2, 耿华^1,2, 谭小弟^1,2,3,*
1安和罗伯特.卢瑞儿童医院儿科系，儿科消化、肝脏与营养分部，胃肠和肝脏炎症研究中心，芝加哥，伊利诺伊州 60611，美国；²西北大学芬伯格医学院儿科系，芝加哥，伊利诺伊州 60611，美国；³西北大学芬伯格医学院病理系，芝加哥，伊利诺伊州 60611，美国
摘要
目前，由肠上皮细胞死亡引发的肠损伤仍然是危险且难以预测的严重疾病之一。肠上皮细胞、免疫系统和微生物组之间相互关联以维持正常肠道稳态和肠屏障的完整性。在微生物入侵时，肠上皮细胞进入死亡程序以维持肠上皮功能，并且保持其持续更新能力，维护组织稳态。但是脱离稳态的肠上皮细胞死亡会导致肠通透性增加和肠屏障功能障碍，导致多种急性和慢性肠道疾病，例如肠缺血/再灌注、败血症、炎症性肠病(inflammatory bowel diseases, IBD)，坏死性小肠结肠炎(necrotizing enterocolitis, NEC)等。在病理生理状态下，过量的肠上皮细胞凋亡性死亡导致慢性炎症状态，而后转向坏死性凋亡细胞死亡机制，其诱导的病理特征比细胞凋亡的情况下更多，此外还可能诱导其它溶细胞性死亡机制，例如细胞焦亡和铁凋亡，从而增加肠道疾病的病理指征。但是，目前关于慢性肠道疾病中肠上皮细胞死亡机制的研究仍然存在空白。目前亟需对慢性肠道疾病(包括败血症，IBD，NEC和肠缺血/再灌注)中特定的细胞死亡机制进行深入了解，以开发针对此类疾病的新型的有效治疗策略。本文旨在综述肠上皮细胞不同死亡机制(例如细胞凋亡，细胞坏死，坏死性凋亡，细胞焦亡和铁凋亡)在急、慢性肠道疾病中的研究进展。
关键词： 肠上皮细胞; 细胞凋亡; 坏死性凋亡; 细胞焦亡; 铁凋亡; 肠道疾病
分类号：Q25

Cell death of intestinal epithelial cells in intestinal diseases
Saravanan Subramanian^1,2, Hua Geng^1,2, Xiao-Di Tan^1,2,3,*
1Center for Intestinal and Liver Inflammation Research, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois 60611, USA；²Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA；³Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
Abstract
Gut injury continues to be the devastating and unpredictable critical illness associated with increased cell death of intestinal epithelial cells (IECs). The IECs, immune system and microbiome are the interrelated entities to maintain normal intestinal homeostasis and barrier integrity. In response to microbial invasion, IEC cell death occurs to maintain intestinal epithelium function and retain the continuous renewal and tissue homeostasis. But the imbalance of IEC cell death results in increased intestinal permeability and barrier dysfunction that leads to several acute and chronic intestinal diseases, such as intestinal ischemia/reperfusion (I/R), sepsis, inflammatory bowel diseases (IBD), necrotizing enterocolitis (NEC), etc. During the pathophysiological state, the excessive IEC apoptotic cell death leads to a chronic inflammatory condition, later switches to necroptotic cell death mechanism that induces more pathological features than apoptosis and may also induce other lytic cell death mechanisms like pyroptosis and ferroptosis to increase the pathogenesis of the intestinal diseases. But still, there remains gaps in the fundamental knowledge about the IEC cell death mechanisms in chronic intestinal diseases. Together, a deep understanding of the specific cell death mechanisms underlying chronic intestinal diseases, including sepsis, IBD, NEC, and intestinal I/R, is desperately needed to develop emerging novel promising therapeutic strategies. This review aims to show how the acute and critical illness in the gut are driven by IEC cell death mechanism, such as apoptosis, necrosis, necroptosis, pyroptosis, and ferroptosis.
Key words: intestinal epithelial cells; apoptosis; necroptosis; pyroptosis; ferroptosis; intestinal diseases

收稿日期：2019-10-25　　录用日期：2020-03-05
通讯作者：谭小弟　　E-mail: xtan@northwestern.edu
DOI: 10.13294/j.aps.2020.0039
引用本文：
Saravanan Subramanian, 耿华, 谭小弟. 肠道疾病中肠上皮细胞的死亡[J]. 生理学报 2020; 72 (3): 308-324.
Saravanan Subramanian, Hua Geng, Xiao-Di Tan. Cell death of intestinal epithelial cells in intestinal diseases. Acta Physiol Sin 2020; 72 (3): 308-324



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