Agmatine induces gastric protection against ischemic injury by reducing vascular permeability in rats

作者：Al Masri Abeer A; El Eter Eman^*

来源：World Journal of Gastroenterology, 2012, 18(18): 2188-2196.

DOI：10.3748/wjg.v18.i18.2188

• Ischemia reperfusion injury
• Agmatine
• Wortmannin
• Vascular permeability
• Monocyte chemoattractant protein-1
• Stomach
• Vascular endothelial growth factor

AIM: To investigate the effect of administration of agmatine (AGM) on gastric protection against ischemia reperfusion (I/R) injury. %26lt;br%26gt;METHODS: Three groups of rats (6/group); sham, gastric I/R injury, and gastric I/R + AGM (100 mg/kg, i.p. given 15 min prior to gastric ischemia) were recruited. Gastric injury was conducted by ligating celiac artery for 30 min and reperfusion for another 30 min. Gastric tissues were histologically studied and immunostained with angiopoietin 1 (Ang-1) and Ang-2. Vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1) were measured in gastric tissue homogenate. To assess whether AKt/phosphatidyl inositol-3-kinase (PI3K) mediated the effect of AGM, an additional group was pretreated with Wortmannin (WM) (inhibitor of Akt/PI3K, 15 mu g/kg, i.p.), prior to ischemic injury and AGM treatment, and examined histologically and immunostained. Another set of experiments was run to study vascular permeability of the stomach using Evan%26apos;s blue dye. %26lt;br%26gt;RESULTS: AGM markedly reduced Evan%26apos;s blue dye extravasation (3.58 +/- 0.975 mu g/stomach vs 1.175 +/- 0.374 mu g/stomach, P %26lt; 0.05), and VEGF (36.87 +/- 2.71 pg/100 mg protein vs 48.4 +/- 6.53 pg/100 mg protein, P %26lt; 0.05) and MCP-1 tissue level (29.5 +/- 7 pg/100 mg protein vs 41.17 +/- 10.4 pg/100 mg protein, P %26lt; 0.01). It preserved gastric histology and reduced congestion. Ang-1 and Ang-2 immunostaining were reduced in stomach sections of AGM-treated animals. The administration of WM abolished the protective effects of AGM and extensive hemorrhage and ulcerations were seen. %26lt;br%26gt;CONCLUSION: AGM protects the stomach against I/R injury by reducing vascular permeability and inflammation. This protection is possibly mediated by Akt/PI3K.

• 出版日期2012-5-14