Zhang Hong-Yi, Wang Fang, Chen Xuyong, Meng Xinrao, Feng Chenzhao, Feng Jie-Xiong
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China.
Department of Neurology, The Central Hospital of Wuhan, Huazhong University of Science and Technology, Wuhan, 430014, China.
Pediatr Surg Int. 2020 Jan;36(1):81-91. doi: 10.1007/s00383-019-04555-5. Epub 2019 Sep 20.
The roles of commensal bacteria after intestinal ischemia and reperfusion (IIR) are unclear. In current study, we aim to investigate the effects and underlying mechanisms of commensal bacteria in injury and epithelial restitution after IIR.
Commensal gut bacteria were deleted by broad-spectrum antibiotics in mice. IIR was induced by clamping superior mesenteric artery. Intestinal injury, permeability, epithelial proliferation, and proinflammatory activity of mesenteric lymph were investigated.
Commensals deletion improved mice survival in the early phase, but failed to improve the overall survival at 96 h after IIR. Commensals deletion reduced proliferation of intestinal epithelial cells (IEC) and augmented proinflammatory activity of mesenteric lymph after IIR. Lipopolysaccharides (LPS) supplement promoted IEC proliferation and improved survival in mice with commensals deletion after IIR. LPS induced production of prostaglandin E2 (PGE2) in mucosa via toll-like receptor 4-NFκB-cyclooxygenase 2 pathway. PGE2 enhanced IEC proliferation in vivo, which was preceded by activation of Akt and extracellular signal-regulated kinase (ERK) 1/2. Blocking of EGFR, PI3K/Akt activity abolished LPS-induced IEC proliferation.
Commensal bacteria are essential for epithelial restitution after IIR, which enhance IEC proliferation via induction of PGE2.
肠道缺血再灌注（IIR）后共生菌的作用尚不清楚。在本研究中，我们旨在探讨共生菌在IIR后损伤和上皮修复中的作用及潜在机制。
用广谱抗生素清除小鼠肠道共生菌。通过夹闭肠系膜上动脉诱导IIR。研究肠道损伤、通透性、上皮细胞增殖以及肠系膜淋巴的促炎活性。
清除共生菌可提高小鼠早期存活率，但不能提高IIR后96小时的总体存活率。清除共生菌可减少IIR后肠道上皮细胞（IEC）的增殖，并增强肠系膜淋巴的促炎活性。补充脂多糖（LPS）可促进IEC增殖，并提高IIR后清除共生菌小鼠的存活率。LPS通过Toll样受体4-NFκB-环氧化酶2途径诱导黏膜中前列腺素E2（PGE2）的产生。PGE2在体内增强IEC增殖，这之前Akt和细胞外信号调节激酶（ERK）1/2被激活。阻断表皮生长因子受体（EGFR）、磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/Akt）活性可消除LPS诱导的IEC增殖。
共生菌对IIR后的上皮修复至关重要，其通过诱导PGE2增强IEC增殖。
