Yang Hua, Wildhaber Barbara, Tazuke Yuko, Teitelbaum Daniel H
Department of Surgery, University of Michigan Medical School, C. S. Mott Children's Hospital, Ann Arbor, USA.
JPEN J Parenter Enteral Nutr. 2002 Nov-Dec;26(6):333-40; discussion 340-1. doi: 10.1177/0148607102026006333.
Keratinocyte growth factor (KGF) increases intestinal growth and is expressed by intestinal intraepithelial lymphocytes (IEL). Because total parenteral nutrition (TPN) leads to villus atrophy and a loss of epithelial function, we hypothesized that KGF administration could reverse these changes.
Mice were randomized into three groups: oral feeding (Control); TPN; or TPN with recombinant human KGF. Mice were killed at 7 days, and the small bowel was harvested for histology, DNA, and protein content analysis. Epithelial cell proliferation was studied by 5-bromo-2-deoxyuridine (BrdU) incorporation, and apoptosis was detected by flow cytometry with Annexin V staining. Epithelial ion transport function was studied by Ussing chambers. Epithelial barrier function was assessed with transepithelial resistance and transmural passage of 3H-mannitol. Epithelial KGF receptors expression was studied by using reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot.
TPN decreased intestinal DNA, protein content, villus height, and crypt cell proliferation. TPN also resulted in an increase in epithelial cell apoptosis. KGF administration significantly stimulated the recovery of mucosal structures including intestinal protein and DNA content, villus height, and crypt cell proliferation, and decreased epithelial apoptosis. KGF also up-regulate the epithelial KGF receptor expression. Moreover, KGF attenuated the TPN-induced increase in ion transport and increased the epithelial barrier function.
KGF administration reversed many of the adverse epithelial changes associated with TPN administration. Additionally, KGF up-regulated epithelial KGF receptor expression. It is possible that KGF may have a therapeutic efficacy in patients who are receiving TPN.
角质形成细胞生长因子（KGF）可促进肠道生长，由肠道上皮内淋巴细胞（IEL）表达。由于全肠外营养（TPN）会导致肠绒毛萎缩和上皮功能丧失，我们推测给予KGF可逆转这些变化。
将小鼠随机分为三组：经口喂养（对照组）；TPN组；或TPN联合重组人KGF组。7天后处死小鼠，采集小肠进行组织学、DNA和蛋白质含量分析。通过5-溴-2-脱氧尿苷（BrdU）掺入研究上皮细胞增殖，采用膜联蛋白V染色的流式细胞术检测细胞凋亡。使用尤斯灌流小室研究上皮离子转运功能。通过跨上皮电阻和3H-甘露醇的透壁通量评估上皮屏障功能。采用逆转录聚合酶链反应（RT-PCR）和蛋白质印迹法研究上皮KGF受体的表达。
TPN降低了肠道DNA、蛋白质含量、绒毛高度和隐窝细胞增殖。TPN还导致上皮细胞凋亡增加。给予KGF可显著促进黏膜结构的恢复，包括肠道蛋白质和DNA含量、绒毛高度以及隐窝细胞增殖，并减少上皮细胞凋亡。KGF还上调上皮KGF受体的表达。此外，KGF减弱了TPN诱导的离子转运增加，并增强了上皮屏障功能。
给予KGF可逆转许多与TPN相关的不良上皮变化。此外，KGF上调上皮KGF受体的表达。KGF可能对接受TPN的患者具有治疗效果。
