Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
PLoS One. 2012;7(9):e44772. doi: 10.1371/journal.pone.0044772. Epub 2012 Sep 13.
Intestinal ischemia/reperfusion (I/R) induces the desquamation of the intestinal epithelium, increases the intestinal permeability, and in patients often causes fatal conditions including sepsis and multiple organ failure. Keratinocyte growth factor (KGF) increases intestinal growth, although little is known about KGF activity on intestinal function after intestinal I/R. We hypothesized that KGF administration would improve the intestinal function in a mouse model of intestinal I/R.
Adult C57BL/6J mice were randomized to three groups: Sham, I/R group and I/R+KGF group. Mice were killed on day 5, and the small bowel was harvested for histology, wet weight, RNA and protein content analysis. Epithelial cell (EC) proliferation was detected by immunohistochemistry for PCNA, and apoptosis was determined by TUNEL staining. The expressions of Claudin-1 and ZO-1 were detected by immunohistochemistry. Epithelial barrier function was assessed with transepithelial resistance (TER).
KGF significantly increased the intestinal wet weight, contents of intestinal protein and RNA, villus height, crypt depth and crypt cell proliferation, while KGF resulted in the decrease of epithelial apoptosis. KGF also stimulated the recovery of mucosal structures and attenuated the disrupted distribution of TJ proteins. Moreover, KGF attenuated the intestinal I/R-induced decrease in TER and maintained the intestinal barrier function.
KGF administration improves the epithelial structure and barrier function in a mouse model of intestinal I/R. This suggests that KGF may have clinical applicability.
肠缺血/再灌注（I/R）会导致肠上皮脱落，增加肠道通透性，在患者中常导致包括脓毒症和多器官衰竭在内的致命情况。角质细胞生长因子（KGF）可促进肠生长，但关于 I/R 后 KGF 对肠功能的作用知之甚少。我们假设 KGF 给药会改善 I/R 后肠功能。
成年 C57BL/6J 小鼠随机分为三组：Sham 组、I/R 组和 I/R+KGF 组。第 5 天处死小鼠，取小肠进行组织学、湿重、RNA 和蛋白质含量分析。通过增殖细胞核抗原（PCNA）免疫组化检测上皮细胞（EC）增殖，通过 TUNEL 染色检测细胞凋亡。通过免疫组化检测 Claudin-1 和 ZO-1 的表达。通过跨上皮电阻（TER）评估上皮屏障功能。
KGF 显著增加了肠道湿重、蛋白质和 RNA 含量、绒毛高度、隐窝深度和隐窝细胞增殖，同时 KGF 减少了上皮细胞凋亡。KGF 还刺激了黏膜结构的恢复，并减轻了 TJ 蛋白分布的破坏。此外，KGF 减轻了 I/R 引起的 TER 降低，并维持了肠道屏障功能。
KGF 给药可改善 I/R 后肠上皮结构和屏障功能。这表明 KGF 可能具有临床应用价值。
