Keratinocyte growth factor improves epithelial structure and function in a mouse model of intestinal ischemia/reperfusion.

Keratinocyte growth factor improves epithelial structure and function in a mouse model of intestinal ischemia/reperfusion.
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角质形成细胞生长因子改善小鼠肠缺血/再灌注模型的上皮结构和功能

DOI:
10.1371/journal.pone.0044772
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Yang H
Yang H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cai Y;Wang W;Liang H;Sun L;Teitelbaum DH;Yang H

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背景肠缺血/再灌注(I/R)导致肠上皮细胞脱屑,增加肠道通透性,在患者中常导致败血症和多器官功能衰竭等致命性疾病。角质形成细胞生长因子(KGF)对肠I/R后肠道功能的影响尚不清楚,但KGF可促进肠生长发育。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。用免疫组织化学方法检测细胞增殖情况,用原位末端标记法检测细胞凋亡率。免疫组织化学方法检测Claudin-1和ZO-1的表达。用跨上皮阻力(TER)评价上皮屏障功能。结果KGF可显著增加模型大鼠肠道湿重、肠道蛋白质和RNA含量、绒毛高度、隐窝深度和隐窝细胞增殖,减少肠上皮细胞凋亡。KGF还可促进粘膜结构的恢复,减轻TJ蛋白分布的紊乱。此外,KGF还可减轻肠I/R所致的TER降低,维持肠屏障功能。结论KGF可改善肠I/R模型小鼠的肠上皮结构和屏障功能,具有一定的临床应用价值。
Background 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. Methods 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). Results 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. Conclusion 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.
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