Mechanisms Of Brain-gut Peptide Ghrelin On Gastrointestinal Dysfunction In Sepsis Patients

Objective To study the effect and mechanism of Brain-gut Peptide-Ghrelin on endocrine function of gastrointestinal tract,damage of gastric mucosal cells,digestive and absorption motility in sepsis in order to provide fundamenta basis for the prevention and treatment of gastroplegia and stress ulcer with Ghrelin and a new and effective treatment channel for intestinal absorption dysfunction.Method 1)Bibliometric analysis of Brain gut Peptide-related literature was used to clarify hot spots and future trends of brain-gut peptide researches.2)Effect of Ghrelin on secretory function,digestive and absorption dynamic function in sepsis rats: Seventy-two male Wistar rats were randomly divided into six groups: sepsis group,control group,sham-operated group,GHRP-6 group,Ghrelin group and Obestatin group.Twelve rats in each group were killed at 2,4,8 and 12 hours after the successful establishment of the model respectively.The stomach was taken and the gastric juice was collected to measure the volume of succus gastricus.Laser Doppler was used to detect the blood flow in greater curvature.3)Thirty-six male Wistar rats were randomly divided into three groups: sham-operated group(injecting saline into abdominal cavity 2 hours before the beginning of the experiment,performing laparotomy after anesthesia without model induction);sepsis group(injecting saline into abdominal cavity 2 hours before the beginning of the experiment,establishing abdominal infection model after cecal ligation and puncture(CLP)];Ghrelin group(2 hours,4 hours after operation).Ghrelin was injected 8 hours after operation,and specimens were collected 12 hours after operation in each group.Apoptotic cells in gastric tissue were detected by TUNEL method.immunohistochemistry,fluorescence quantitative PCR and Western-blot was used to detect the expression of Bcl-2 and Bax protein in the gastric tissue of rats.Flow cytometry was used to detect the effect of Ghrelin on LPS-induced apoptosis of gastric mucosal cells in vitro.Results 1)At present,the research of brain-gut peptide mainly involves the production,properties,physiological function and regulation of brain-gut peptide.The essence of brain-gut peptide is a hormone.Its main physiological functions are regulating gastrointestinal motility,protecting gastrointestinal mucosa and improving gastrointestinal dysfunction.At the same time,it can promote eating and stimulate gastric juice secretion.Brain gut peptide can reduce apoptosis of gastric mucosal cells by increasing gastric mucosal blood flow,promoting gastric contraction and dosedependent.However,those views are still controversial now.2)There was no significant difference in gastric fluid volume between normal control group and sham operation group at each time point(P >0.05).Compared with shamoperated group,the gastric fluid volume in sepsis group decreased at 2,8 and 12 hours after intervention(all P < 0.05),but there was no significant difference at 4 hours after intervention(P >0.05).Compared with sham-operated group and sepsis group,gastric fluid volume in Ghrelin group increased significantly from 2 hours after intervention(all P <0.05),and was time-dependent.Compared with sham-operated group,sepsis group and Ghrelin group,gastric fluid volume in GHRP-6 group increased significantly 2 hours after intervention(P <0.05),and was time-dependent.Obestain group compared with other groups,there were significant differences at each time point(P <0.05).3)Ghrelin mRNA level in CLP group was significantly lower than that in sham operation group at 2 hours after operation.Compared with sham-operated group,Ghrelin protein level in gastric tissue and systemic circulation of rats in CLP group decreased 20 hours after operation.The application of Ghrelin significantly increased the level of Ghrelin in gastric mucosa and serum.The levels of cytokines,including TNF-a,IL-6 and IL-1beta,in circulatory and gastric tissues of CLP group were significantly higher than those of sham operation group,while Ghrelin treatment could reverse the increase induced by CLP.Apoptotic cells were observed in all three groups.TUNEL mean optical density(MOD)of gastric tissue cells in sepsis group and Ghrelin treatment group was higher than that in sham group.The difference was statistically significant.MOD in Ghrelin group was significantly lower than in CLP group(P < 0.05).Compared with sham group,Bcl-2 mRNA in gastric tissue of rats in CLP group and Ghrelin group was significantly lower than that in sham group,and Bax-mRNA was significantly higher than that in sham group(P < 0.05);compared with CLP group,Bcl-2 mRNA in gastric tissue of rats in Ghrelin group was significantly higher and Baxmrna was significantly lower(P <0.05).Compared with sham group,Bcl-2 in gastric tissue of CLP group and Ghrelin group was significantly lower than that of normal group,and Bax was significantly higher than that of sham group(P <0.05).After stimulation of gastric epithelial cells using LPS in vitro,the percentage of apoptotic cells in gastric epithelial cells without Ghrelin treatment was significantly higher than that in Ghrelin treatment group.Conclusion Most researchers believe that Brain-gut Peptide-Ghrelin can regulate gastrointestinal function,promote the repair of gastric mucosa in sepsis and reduce the occurrence of intestinal barrier disorders.Our results showed that the expression of Bcl-2 decreased and Bax increased in gastric tissues during sepsis,and Ghrelin could up-regulate the expression of Bcl-2 and reduce the expression of Bax.Ghrelin can effectively regulate gastrointestinal function through nerve-body fluid pathway,thereby promoting gastric juice secretion,improving gastric mucosal blood flow perfusion,and alleviating gastric tissue damage.