Heparin-binding epidermal growth factor-like growth factor improves intestinal barrier function and reduces mortality in a murine model of peritonitis.
Heparin-binding epidermal growth factor-like growth factor improves intestinal barrier function and reduces mortality in a murine model of peritonitis.
复制标题
肝素结合表皮生长因子样生长因子可改善小鼠腹膜炎模型的肠道屏障功能并降低死亡率。
DOI：
10.1016/j.surg.2012.04.002
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发表时间：
2013
期刊：
影响因子：
3.8
通讯作者：
Besner,GailE
中科院分区：
文献类型：
--
作者：
Yang,Jixin;Radulescu,Andrei;Chen,Chun-Liang;Zhang,Hong-Yi;James,IyoreO;Besner,GailE
背景与细菌性腹膜炎相关的发病率和死亡率仍然很高。肝素结合表皮生长因子（EGF）样生长因子（HB-EGF）是一种有效的肠道细胞保护剂。方法将HB-EGF（-/-）基因敲除（KO）小鼠及其野生型（WT）小鼠分别进行假手术、盲肠结扎穿孔（CLP）或CLP + HB-EGF治疗（800 μg/kg IP/d）。检测绒毛长度、肠通透性、肠上皮细胞（IEC）凋亡、腹腔液（PF）和肠系膜淋巴结（MLN）细菌负荷、炎性细胞因子水平和存活率。（1.37 ± 0.13 vs 1.96 ± 0.4相对单位; P <0.03），肠通透性增加（17.01 ± 5.18 vs 11.50 ± 4.67 nL/min/cm 2; P <0.03），IEC凋亡指数增加（0.0093 ± 0.0033 vs 0.0016 ± 0.0014; P <0.01），PF中细菌计数增加（25，313 ± 17，558 vs 11，955 ± 6，653菌落形成单位[CFU]/mL; P < .05）和MLN（19，009 ± 11，200 vs 5，948 ± 2，988 CFU/mL/g; P < .01）。对暴露于CLP的WT和HB-EGF KO小鼠给予HB-EGF可导致MLN中的绒毛长度显著增加，肠通透性、IEC凋亡和细菌计数显著降低（P <0.05）。HB-EGF基因敲除小鼠的生存率明显提高（P <0.05）。结论：HB-EGF基因敲除小鼠对腹膜炎引起的肠损伤的易感性增加，可被HB-EGF逆转。这些结果支持HB-EGF在腹膜炎诱导的脓毒症中的保护作用。
BACKGROUNDThe morbidity and mortality associated with bacterial peritonitis remain high. Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a potent intestinal cytoprotective agent. The aim of this study was to evaluate the effect of HB-EGF in a model of murine peritonitis.METHODSHB-EGF(−/−)knockout (KO) mice and their HB-EGF(+/+)wild-type (WT) counterparts were subjected to sham operation, cecal ligation and puncture (CLP), or CLP with HB-EGF treatment (800 μg/kg IP daily). Villous length, intestinal permeability, intestinal epithelial cell (IEC) apoptosis, bacterial load in peritoneal fluid (PF) and mesenteric lymph nodes (MLN), inflammatory cytokine levels, and survival were determined.RESULTSAfter exposure to CLP, HB-EGF KO mice had significantly shorter villi (1.37 ± 0.13 vs 1.96 ± 0.4 relative units; P < .03), increased intestinal permeability (17.01 ± 5.18 vs 11.50 ± 4.67 nL/min/cm2; P < .03), increased IEC apoptotic indices (0.0093 ± 0.0033 vs 0.0016 ± 0.0014; P < .01), and increased bacterial counts in PF (25,313 ± 17,558 vs 11,955 ± 6,653 colony forming units [CFU]/mL; P < .05) and MLN (19,009 ± 11,200 vs 5,948 ± 2,988 CFU/mL/g; P < .01) compared with WT mice. Administration of HB-EGF to WT and HB-EGF KO mice exposed to CLP led to significantly increased villous length and decreased intestinal permeability, IEC apoptosis and bacterial counts in MLN (P < .05). Survival of HB-EGF KO mice subjected to CLP was significantly improved with administration of HB-EGF (P < .05).CONCLUSIONHB-EGF gene KO increases susceptibility to peritonitis-induced intestinal injury, which can be reversed by administration of HB-EGF. These results support a protective role of HB-EGF in peritonitis-induced sepsis.