Research On The Protective Effect Of Ulinastatin On The Intestinal Barrier Of The Exertional Heatstroke Rat

Objective:To establish the stable exertion heatstroke rat model,observe theUlinastatin’s effect on the intestinal permeability and intestinal mucosal immunestatus of exertional heatstroke rat. And explore the protective effect of differentdoses of Ulinastatin on intestinal mucosal mechanical barrier,immune barrier.Method:30SD rats were selected to established exertional heatstroke animalmodel using experimental animal treadmill and Environement Training Lab settingthe temperature to (40±0.5)℃，humidity to70%±5%.Then measured serum CK、ALT、AST, observed the pathological changes of quadriceps by hematoxylin-eosinstaining to prove the scientificity.After modeling, recorded the onset time, thechange of rectal temperature, survival time and mortality rate.On this basis,134SD rats were randomly divided into four groups:blankcontrol-group(Normal-Control,n=8),exertional heatstroke group (EHS,n=42),large-dose ulinastatin treatment group(LUTI-EHS,n=42),small-dose ulinastatintreatment group(SUTI-EHS,n=42).We used heat stress complicated with highintensity exercise to make EHS happen. After modeling and treatment, we randomlytook10rats from EHS、LUTI-EHS、SUTI-EHS to observe survival time andmortality rate, the remaining rats were divided into four subgroups(n=8) according tothe observation time(30min、2h、4h、6h).Plucked blood by carotid artery to observethe Ulinastatin’s impact on the intestinal permeability(plasma DAO activity andD-lactate concentration) of exertional heatstroke rat, detect the changes of intestinaltissue morphology and immunohistochemistry.And compare the protective effect ofdifferent doses of Ulinastatin on intestinal mucosal mechanical barrier, immunebarrier and survival time, mortality rate.Result:(1)The average onset time of exertional heatstroke group was57.8±18.9min,8h mortality rate was100%,and the serum CK、ALT、AST significantly increased. Skeletal muscle of model group: Eye view: skeletal texture unclear, tissuetoughness; endoscopic view: the structure of the muscle fibers occurs extensiverupture, and infiltrated with inflammatory cell.(2)This experiment showed that the survival time of large-dose and small-doseUlinastatin group was higer than the exertional heatstroke group. Besides themortality rate of two group was lower than the exertional heatstroke group.(3)In the four time points, the DAO activity and D-lactate concentration of EHSLUTI-EHS、SUTI-EHS groups were first increased then decreased. Ulinastatincould significantly reduce serum DAO activity and D-lactate concentration, reducedintestnal mucosal injury,but also could see inflammatory cell infiltration and vasculardilation.After onset,the intestinal CD4+T lymphocyte percentage decreased, CD8+Tlymphocyte percentage decreased,and Ulinastatin could increase CD4+T lymphocytepercentage, decrease CD8+T lymphocyte percentage. Besides,the high-dose treatme-nt is better than small-dose.Conclusion: Ulinastatin can extend survival time of exertional heatstroke rats,inhibited increase permeability of the intestinal mucosal barrier, reduce the damageof mucosal barrier and improve mucosal immune regulation function.