| BackgroundAcute gastric mucosal injury(AGML)is a common clinical complications with high mortality.The process is regulated by the multi-factor and multi-way,which is not fully clear.It is meaningful to explore the risk factors and seek for targets which can intervene the process.It is confirmed that excessive and sustained damage stress is the most important factor to induce AGML.,Difficult and complex surgery is one of the main stressors of AGML;Small and medium-sized surgery are not listed as risk factors of AGML,and also not listed as risk factors which can increase the probability of AGML bleeding.However,in clinic,Small and medium-sized surgery can increase the incidence of AGML in high-risk populations and aggravate illness.So,we propose to research whether medium-sized surgery as a kind of harmful stress can aggravate the already existing gastric mucosal damage and delay the repair.In recent years,The transient receptor potential vanilloid 1(TRPV1)and acid-sensing ion channel 3(ASIC3)in stomach tissue as chemical receptor is increasingly attention.TRPV1 is widely expressed in gastric mucosa epithelial cells,It is thought to affect mucosal defense mechanism by adjust the gastric mucosal blood flow,gastric acid secretion,gastric motivation and other factors which can change gastric tissue microenvironment;TRPV1 participate in the regulation of healing of vascular endothelial cells,corneal epithelium cells and myocardial cell injury.ASIC3 is one of the members of acid sensitive ion channels family,a small amount of research shows that ASIC3 are distributed in esophagus,colon and stomach tissue which play an important role in the process of information processing.Our previous studies have found that TRPV1/ASIC3 played an significant role in stress-induced gastric mucosa damage.Our study will explore the expression and effect of TRPV1/ASIC3 in healing of acute gastric mucosal injury.In addition,TRPV1/ASIC3 channels which also distribute in sensory nerve system can obviously intervene acute postoperative pain.Our previous works have observed that sufentanil pretreatment can activate TRPV1 in gastric mucosa of AMGL rat to protect gastric mucosa,ASIC3 antagonists pretreatment can reduce gastric mucosa oxidative damage.So we speculate that superficial surgical trauma and acute pain may change the activity of TRPV1/ASIC3 in gastric mucosal cells to participate in gastric mucosal injury and repair.Purposes1.Expression and effects of TRPV1 in gastric mucosal during healing of stress-induced gastric mucosal injury;2.Effects of SMIR in healing of acute gastric mucosal lesions and expression of TRPV1/ASIC3.The objective of this study was to raise the acknowledge of TRPV1/ASIC3 in pathophysiological process of gastric mucosal injury and healing,and provide new ideas for control perioperative stress and prevention of AGML.Methods1.50 healthy Wistar rats were randomly divided into normal controlled group(group NC,n=10),WIRS model group(group WIRS,n=10),2h after WIRS group(group W2 h n=10,1d after WIRS group(group W1 d,n=10)and 3d after WIRS group(group W3 d,n=10).The general extent of gastric mucosal injury was observed and assessed for gastric mucosal ulcer index(UI).Rectal temperature,water content of stomach tissue,intragastric pH,Serum SOD,MDA and SOD/MDA ratio were measured,the expressions of TRPV1 mRNA and ASIC3 mRNA in gastric mocusal were assessed by Real-time Quantitative PCR,immunohistochemistry was performed to detect the localization of TRPV1/ASIC3 and mesure the mean density of TRPV1.2.56 healthy Wistar rats were randomly divided into normal controlled group(group NC,n=8)and experimental group,The experimental group was divided into WIRS group(group WIRS,n=24)and SMIR after WIRS group(group WS,n=24),Group WIRS is divided into two hours after modeling group(group W2 h,n=8),1 day(group W1 d,n=8),3 days group(group W3 d,n=8),Group WS similarly divided into group WS2 h,group WS1 d and group WS3 d,Each group 8 rats.Experiment with the second part.Results1.Compared with group NC,rectal temperature of group WIRS and W2 h was obviously lower(P < 0.05),group W1 d and W3 d returned to normal;Compared with group NC,the group WIRS showed obvious gastric mocusal injure with higher UI(P < 0.05),There was no statistical difference between group W2 h with WIRS,group W1 d which was higher than group NC was lower than group WIRS and W2h(P < 0.05),group W3 d which had no statistical difference with group NC was lower campared with group WIRS,W2 h and W1d(P < 0.05);water content of stomach tissue of group WIRS,W2 h,W1d and W3 d were all higher than group NC(P < 0.05),Group WIRS and W2 h were the highest,there was no statistical difference between them,group W1 d which decreased campared with them had no statistical difference with group W1d;Compared with group NC,WIRS,gastric pH of group WIRS and W2 h significantly decreased(P < 0.05),group W1 d and W3 d increased and were higher than group WIRS,W2 h and NC(P < 0.05),no statistical difference between the two groups;compared with NC group,the serum SOD,MDA,SOD/MDA of group WIRS and W2 h were higher(P < 0.05),group W1 d and W3 d had no statistical difference;Respectively compared with group WIRS and W2 h,the three indicators had no statistical differences in group W1 d,SOD reduced in W3 d,SOD/MDA increased(P < 0.05)and MDA had no obvious changes,compared with group W1 d,SOD of group W3 d reduced(P < 0.05),the other two had no statistical difference;TRPV1 in gastric mocusal decreased after modeling(P < 0.05),reached the low peak at the first day and raised to normal level 3 days later,TRPV1 expression in gastric pit peripheral cell at focus of damage reduced the most.ASIC3 in gastric mocusal increased after modeling(P < 0.05),then decreased and reached the low peak at the first day,didn't raised to normal level 3 days later.ASIC3 was highly correlated with the PH and rectal temperature.2.Compared with group WIRS,mocusal damage of group WIRS was aggravating,repaired delay.Factorial analysis shows that the UI,water content,SOD,MDA,gastric mucosal TRPV1 and ASIC3 respectively in the treatment groups,each time point,interaction effect have statistical difference(P < 0.05);Gastric pH,SOD and MDA in each time point,interaction effect have statistical difference,no statistical difference between treatment groups.The trend of each index of SMIR group at each time point is similar with WIRS group.UI of WS group was higher than WIRS group in the healing of AGML(P < 0.05);tissue water content of WS group was higher than WIRS group in 2 hours and 1 day after stress(P < 0.05),No statistical differences between the two 3 days later.;SOD/MDA of group WS was significantly lower than group WIRS(P < 0.05)at 2 hours after stress,no obvious difference between the two groups 1 day later,group WS was higher than group WIRS 3 days later(P < 0.05);TRPV1 of WS group was below the WIRS group in 2 hours,1 day and 3 days after stress(P < 0.05);ASIC3 of group WS which was lower than WIRS group at 2 hours after stress were higher than group WIRS in 1 day and 3 days(P < 0.05).TRPV1 was associated with UI and SOD/MDA,ASIC3 is highly related with intragastric pH.Conclusion:1.In the healing of acute gastric mucosal,the expression of gastric TRPV1 showed a trend from decline to rise,which was harmful to ulcer healing.the expression of gastric ASIC3 showed a trend from decline after rising again increased.TRPV1/ASIC3 may be involved in the regulation of healing of AGML.2.SMIR aggravates gastric mucosal injury and delays repair in WIRS model,TRPV1 expression in gastric mocusal of AGML model is inhibited,TRPV1 may participate in further damage and healing on gastric mucosa of AGML rats;After gastric mucosal injury early,SMIR has no impact on expression of ASIC3 in gastric mucosa of AGML rat,inhibitory effect is reduced in the late. |
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