| 共同演者 |
Chan Francis KL（Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong）, Cheung Maggie SH（Department of Surgery, The Chinese University of Hong Kong, Hong Kong）, Yu Jun（Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong）, Lau James YW（Department of Surgery, The Chinese University of Hong Kong, Hong Kong） |
| 抄録 |
Background：Aspirin has been reported to induce serious small bowel ulceration and bleeding. To date, there is no effective prevention for aspirin-induced enteropathy. Lysophosphatidic acid（LPA）, a metabolite from PC has been found to maintaining the integrity of gastrointestinal tract epithelium by inhibiting apoptosis. PC-aspirin has been developed to reduce gastric toxicity of aspirin. We hypothesized that PC-aspirin would reduce aspirin-induced small bowel injury.
Methods：Sprague-Dawley rats received intra-duodenal administration of either PC-aspirin（100mg, n=12）, plain aspirin（100mg, n=12）or vehicle（1ml 2% methycellulose, n=12）, and euthanized after 90 minutes. Small bowel injury was assessed by lesion area, vascular permeability, intestinal hemoglobin concentration and histological change. Secondary endpoints included expression of LPA2 receptor, apoptotic index, TLR4, MyD88, COX-2, NF-κΒp50 and prostaglandin E2（PGE2）of the small bowel.
Results：Comparing to plain aspirin-treated rats, PC-aspirin caused significantly fewer injuries in the small bowel mucosa（P=0.003 for lesion area, P=0.003 for vascular permeability, P=0.044 for intestinal hemoglobin concentration, P=0.045 for histological change）. Immunohistochemical staining and western blot（P=0.044）showed that LPA2-positive cells were strongly expressed in surface-lining of small bowel mucosa in the control and PC-aspirin groups but not in the plain aspirin group. PC-aspirin treated rats had significantly decreased apoptotic index in the small bowel（P＜0.001 for TUNEL staining, P=0.007 for cleaved caspase-3）. The tissue expression of TLR4, MyD88, NF-κΒp50 and COX-2 were increased while PGE2 was decreased in both plain aspirin and PC-aspirin groups.
Conclusion：
PC-aspirin significantly decreased small bowel injury possibly through increased expression of LPA2 receptors and decreased apoptosis.
Key words：Phosphatidylcholine, aspirin, small bowel injury |
