The role of apelin on formation and healing of ischemia reperfusion induced gastric ulcer

The aim of the study was to determine the possible role of apelin on formation and healing mechanisms of ischemia reperfusion (I/R) induced mucosal lesions. For this purpose, 1.Control group, 2.Sham group, 3.I/R groups (for this group, the animals were sacrificed at five different time points following the I/R. 3a. immediately, 3b. 24 hours later, 3c. 72 hours later, 3d. 120 hours later, 3e. 240 hours later I/R.) 4. F13A (150µg/kg/day) + I/R group, 5. I/R + F13A groups (for this group, the animals were exposed to the I/R and taken apelin antagonist then were sacrificed at four different time points following the I/R. 5a. 24 hours later, 5b. 72 hours later, 5c. 120 hours later, 5d. 240 hours later.). Gastric mucosal blood flow, lesion index, MPO, 4-HNE-MDA, NOx, PGE2, TNF-?, HO activity apelin, VEGF, HO-1 protein expressions and immunoreactivities of Nrf2, HIF-1? and VEGF were measured. Mucosal lesion formation was observed in animals, which are exposed to I/R. It was observed that F13A application before I/R increased mucosal injury. The application of F13A following I/R caused a delay in healing process. Mucosal blood flow decreased in I/R groups, and reached into control levels in healing groups but lower blood flow was observed in all F13A applicated groups. Increased gastric MPO actvity due to I/R was greater in 24 hours later I/R and started to decrease in 72 hours later I/R. High MPO activity was determined in healing process of F13A applicated I/R groups. I/R application caused to increase in 4HNE-MDA levels but 4-HNE-MDA levels reached into control leves in healing groups. No significant difference was detected between F13A aplicated and non applicated healing groups. NOx levels increased due to I/R and decreased even reached into control levels during healing process. However high NOx levels were established in all F13A applicated healing groups. It was observed that decreasing PGE2 levels due to I/R, reached into control levels in healing groups but this increase delayed in F13A applicated healing groups. TNF-? levels in gastric tissue increased due to I/R and decreased gradually in healing groups. Higher TNF-? levels were determined in F13A applicated healing groups compared to non F13A applicated healing groups. Nrf2 immunreactivity decreased due to I/R in muscle and stroma areas of the stomach, no alteration was detected in the other areas. High levels of HO activity and HO-1 protein expression levels were determined in I/R group and 24th hour of healing proces, and levels started to decrease at 120th hour of healing process. No significant difference was detected in HO activities and HO-1 protein levels between F13A aplicated and non applicated healing groups. The increased levels of HIF-1? immun reactivity due to I/R, decreased in healing process. Greater decrease was established in F13A applicated groups. I/R application caused to increase in Apelin protein expression. VEGF protein expression did not changed due to I/R but an increase was detected at 120th and 240th hours following I/R. F13A depressed the increase of VEGF expression in healing groups. In conclusion Apelin has a preventing effect on mucosal lession formation and accelerating effect on healing process. Positive effects of Apelin on gastric mucosa can be explained by the feature of increasing gastric mucosal blood flow, PGE2 production and VEGF expression and also decreasing TNF-? levels. Key words: Apelin, F13A, Ischemia Reperfusion, Gastric Healing, Gastric Mucosal Barrier