| Objective: This study aimed to determine whether ghrelin,orexin-A or nesfatin-1 has a protective effect on gastric mucosa,whether it can alter the healing of chronic gastric ulcer,and their effect on gastric ulcer in diabetic rats.Methods: A chronic gastric ulcer was induced by glacial acetic acid and a gastric ulcer model was established.The effects of intraperitoneal injection of ghrelin,orexin-A and nesfatin-1 on the size of gastric ulcer and marginal blood flow of ulcer were observed.Combined intraperitoneal injection of ghrelin and ghrelin receptor antagonists Dlys3,GHRP or orexin-A and orexin-A receptor antagonist SB-334867,the effects on gastric ulcer area and marginal blood flow of ulcer were observed.The effects of ghrelin,orexin-A or nesfatin-1 on the on gastric ulcer were observed by subcutaneous injection of capsaicin to block sensory afferent fibers,intragastric administration of capsaicin receptor antagonist capsazepine,or intraperitoneal injection of nitric oxide synthase inhibitor L-NNA.Type I diabetic rats were established by intraperitoneal injection of streptozotocin(STZ).The protective effects of intraperitoneal injection of ghrelin,orexin-A or nesfatin-1 on gastric mucosal cells of diabetic rats were observed and compared.Results: Different doses of ghrelin or orexin-Awere injected intraperitoneally,the surface of gastric ulcer in rats decreased and the marginal GBF of ulcer increased(P < 0.05).With the increase of ghrelin injection dose,the area of gastric ulcer decreased gradually,and the marginal GBF of ulcer gradually increased,showing a significant dose dependent relationship(P<0.05~0.01).If intraperitoneal injection of ghrelin and its receptor antagonist D-lys3-GHRP,or orexin-A and its receptor antagonist SB-334867,the effects of ghrelin or orexin-A on gastric mucosal were damage(P<0.05).Pre-subcutaneous injection of capsaicin blocked the stomach sensory afferent nerve,the protective effect of ghrelin,orexin-A or nesfatin-1 on gastric ulcer was weakened,which showed that the area of gastric ulcer increased significantly(P<0.05),and the blood flow at the edge of ulcer decreased significantly(P < 0.05)compared with the corresponding group without capsaicin.However,there was no significant difference in the area of gastric ulcer or the marginal GBF of ulcer with subcutaneous injection of capsaicin(P>0.05).Rats were perfused with 2.5 mg/kg pepper flat to block the capsaicin receptor,weaken the protective effects of ghrelin and orexin-A or nesfatin-1 on gastric ulcer,gastric ulcer area showed significantly increased(P<0.05),GBF significantly reduced the ulcer margin.Intraperitoneal injection of L-NNA+orexin-A or L-NNA+nesfatin-1,the protective effect of orexin-A or nesfatin-1 on gastric ulcers attenuated,the area of gastric ulcer increased significantly(P < 0.05),and the marginal blood flow of ulcer decreased significantly(P < 0.05).Compared with nondiabetic gastric ulcer rats,the healing process of gastric mucosa in diabetic rats was slowed down,and the area of ulcer increased significantly(P < 0.05),and the marginal GBF of ulcer decreased significantly(P < 0.05).Compared with non-diabetic gastric ulcer rats,intraperitoneal injection of orexin-A,ghrelin or nesfatin-1 in diabetic rats,the area of gastric ulcer rats increased significantly(P < 0.05),and the ulcer margin GBF significantly decreased(P < 0.05).In diabetic gastric ulcer rats,orexin-A,ghrelin or nesfatin-1 had no significant protective effect on the gastric mucosa compared with the NS control group(P > 0.05).Conclusion: Ghrelin,orexin-A or nesfatin-1 can promote the healing of chronic gastric ulcer induced by acetic acid,and the effects of ghrelin or orexin-A may be achieved through its receptor signaling pathway.The sensory afferent fibers play an important role in ghrelin,orexin-A or nesfatin-1 on chronic gastric ulcer healing.Nitric oxide is also involved in the healing process of chronic gastric ulcer.Ghrelin,orexin-A or nesfatin-1 have almost no effect on the healing of chronic gastric ulcer in diabetic rats. |
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