Experimental Studies On The Relationship Between Endothelin-1 Gene And Stress Ulcer

Stress Ulcer is a usual complication derived from clinical serious disease,serious trauma and psychosis in clinic.There is a higher incidence and mortality rate. At present,its precise pathogenes is not very clear yet.So the effect of prevention and treatment of SU is not very satisfied. The current studies ascertain that gastric microcirculation disturbance is its main pathophysiological process in the development of SU, and the vasomediators responded for it are not obvious yet. So the study on pathogenesis of SU based on gastric microcirculation disturbance and vasomediate have great theoretic and practical significance.Endothelin-1(ET-1)is a novel endogenous vasoconstrictive peptide and plays great important role in mediating the vessel tension and local micro-circulation.In recent years, studies on the relationship between ET-1 and SU have made many foreign scholars great attention and interest,while there is not any report on it in china .The objective of this study is to explore the role of ET-1 in the pathogenesis of SU,so as to provide theoretic and practical guidement for its clinical prevention and treatment.1.Changes and its significance of plasma and gastric mucosa ET-1 levels,GMBF, UI and ECS in rats with stress ulcer induced by cold-restraint-stress.Objective:To explore the significance of plasma and gastric mucosa endothelin(ET)-1 levels in the development and progression of stress ulcer.Methods:Plasma and gastric mucosa ET-1 levels, the location of the ET-1 expression in gastric mucosa ,gastric mucosa blood flow(GMBF), ulcer index(UI) and endothelial cell space(ECS)were measured by using radioimmunoactive(RIA), immunohistochemistry(IHC),laser doppler flow metre,estimating UI according to"Guth standard" and transmission electron microscopy(TEM)prior to stress and 1,3,6,9,12 hours poststress in cold-restraint-stress- induced ulcer model of rats.Results:Both plasma and gastric mucosa ET-1 cocentrations were increased significantly after stress compared with the control values.ET-1 concentrationsin plasma were increased gradually,and showed a peak at 6 hours poststress and then remained significantly higher than control values (P<0.05), while ET-1 levels in gastric mucosa continued to increase significantly during stress-12hour (P<0.01). In addtion,GMBF was decreased markedly(P<0.01), UI was increased dramatically(P<0.01) poststress. Moreover, there was positive relationship between gastric mucosa ET-1 and UI(r=0.98,P<0.01), negative relationship between gastric mucosa ET-1 and GMBF(r=-0.89,P<0.01). IHC showed that the ET-1 was stained as brownish grains,and localized in the cytoplasma of gastric epithelial cells,vascular endothelium cells,vascular smooth muscule cells and stomach smooth muscle cells around muscularis mucosa in stomach. Furthering,both the proportion of ET-1 positive cells and ET-1 cellular intensity were significantly higher in poststress stomach than in normal stomach of rats. TEM showed that gastric mucosa microvascular endothelial cells got injuried and swelled dramatically(P<0.01),ECS were increased dramatically (P<0.01).Conclusion: These results suggest that gastric mucosa can not only synthesize and secret ET-1 ,but also do it much more significantly in the formation of cold restraint-stress-induced ulcers in rats.The increased endogenous ET-1 may be involved in the development and progresssion of stress ulcer in rats through vasoconstricting,reducing GMBF and increasing ECS, then cause gastric mucosa ischemic lesions—ischemia,erosion,ulceration.2.Expression of ET-1mRNA,ETARmRNA and ECEmRNA in gastric mucosa of CRS ratsObjective :To explore the significance of expression of ET-1mRNA,ETARmRNA and ECEmRNA in CRS rats gastric mucosa in the development and progression of stress ulcer.Methods:Expression levels of ET-1mRNA,ETARmRNA and ECEmRNA in CRS rats gastric mucosa were measured by using RT-PCR(reverse transcription-polymerase chain reaction),dot blot and northern blo...