Effect And Mechanism Of Tiopronin On Cushing’s Ulcer Of Rats After TBI

ObjectiveTo explore the effect and mechanism of tiopronin on Cushing’s ulcer aftertraumatic brain injuryMethodsSeventy-five adult male Sprague-Dawley rats were randomly divided intofive groups: sham-operated group、control group、cimetidine group（3mg/Kg）、low-dose tiopronin group（3mg/Kg）、high-dose tiopronin group（6mg/Kg），and there were fifteen rats in every group. Traumatic brain injury models ofcontrol group、cimetidine group and TPN groups were established according tomodified Feeney’s free-falling method,and2ml of tiopronin wasintraperitoneally injected into TPN groups’rats immediately accroding to theconcentration gradient of tiopronin and at the same time the same content ofcimetidine（3mg/Kg） and normal saline was intraperitoneally injected intocimetidine group and control group rats respectively. Modified neurologicalseverity score was performed12h,24h and36h after traumatic brain injury. Therats were killed at36h after models establishment.Gastric mucosa ulcer wasobserved and the morbidity of Cushing’s ulcer was calculated. The pH value ofgastric juice and the thickness of gastric slime layer were determined.Microscopic pathologic appearance of gastric mucosa was observed. Aenzymoimmunoassay was used to determine the concentration ofprostaglandin E2、malonaldehyde(MDA) and Interleukin-8（IL-8） in the gastricmucosa. mRNA explressions of intereukin-8in gastric mucosa weredetermined by RT-PCR.ResultsAs compared to the sham-operated group, scores of mNSS, malonaldehyde concentration，IL-8concentration and mRNA expressions ofinterleukin-8in gastric mucosa were significantly increased and pH value,thickness of gastric slime layer and prostaglandin E2concentration weresignificantly reduced in the other five groups(P<0.05).Morbidity of Cushing’sulcer, malonaldehyde concentration， IL-8concentration and mRNAexpressions of interleukin-8were significantly reduced and thickness of gastricslime layer, pH value of gastric juice and prostaglandin E2concentration weresignificantly increased in cimetidine group and TPN groups as compared withthose in the control group(P<0.05).Scores of mNSS,morbidity of Cushing’sulcer, malonaldehyde concentration,IL-8concentration and mRNA expressionsof interleukin-8were significantly reduced and thickness of gastric slimelayer,pH value of gastric juice and prostaglandin E2concentration weresignificantly increased in high-dose group as compared with those in thecimetidine group(P<0.05).Conclusion1.Tiopronin could promote neurological functionof the rats after traumaticbrain injury；2.Tiopronin could reduce the morbidity of Cushing’s ulcer；3.Tiopronin could increase the thickness of gastric slime layer and theconcentration of prostaglandin E2concentration,and could inhabit the gastricacid secretion, oxygen free radical reaction and inflammatory reaction causedby IL-8；4.Tiopronin has preventive and therapeutic effects on Cushing’s ulcer andthe mechanism may be related to the above three points；5.Preventive and therapeutic effects of high-dose tiopronin on Cushing’sulcer（6mg/Kg） was better than those of cimetidine（3mg/Kg）.