Hepatocyte growth factor ameliorates inflammatory bowel disease in a rat model.
This study was designed to investigate the benefits of administration of hepatocyte growth factor in a rat model of inflammatory bowel disease. Transfection of the HLA-B27 gene into Fisher rats induces a phenotype similar to inflammatory bowel disease. Fisher rats and HLA-B27 rats were divided into six groups: (1) Fisher, intravenous saline; (2) HLA-B27, intravenous saline; (3) HLA-B27, intravenous hepatocyte growth factor; (4) Fisher, luminal saline; (5) HLA-B27, luminal saline; and (6) HLA-B27, luminal hepatocyte growth factor. Rats received a 14-day infusion through an osmotic pump attached to a catheter positioned in either the jugular vein or the terminal ileum. Rats were evaluated for stool character, and gross and microscopic bowel inflammation. Statistics were analyzed using analysis of variance or the Kruskal-Wallis nonparametric test. A value of P<0.05 was significant. Compared to untreated HLA-B27 rats, intravenous administration of hepatocyte growth factor decreased diarrhea by 41% and microscopic inflammation by 54% (P<0.05). Luminal hepatocyte growth factor exposure decreased total bowel lesions by 53% and microscopic inflammation by 40% compared to untreated HLA-B27 rats (P<0.05), but it did not have an effect on diarrhea. Administration of hepatocyte growth factor ameliorates many of the features of bowel disease in this rat model and theoretically could have therapeutic applications in the management of inflammatory bowel disease in humans.
Arthur
L Grier
LG
Department of Surgery, A.I. duPont Hospital for Children, Wilmington Delaware 19803, USA.
Kuenzler
Keith A
KA
Schwartz
Marshall Z
MZ
D000287:Administration, Topical; D000818:Animals; D005260:Female; D006133:Growth Substances / Q000008:administration & dosage*; D015796:HLA-B27 Antigen / Q000276:immunology; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D007262:Infusions, Intravenous; D007422:Intestines / Q000187:drug effects*; D023421:Models, Animal; D051381:Rats; D011916:Rats, Inbred F344
D006133:Growth Substances; D015796:HLA-B27 Antigen; D017228:Hepatocyte Growth Factor