Mechanism Of Ulinastatin In Reducing Lung Inflammatory Injury In Rats With Traumatic Hemorrhagic Shock

Objective:To investigate the effect of ulinastatin on the inflammatory mediators and their signaling pathways mi R-146a/TLR4/NF-?B in rats with hemorrhagic shockMethods : Seventy-two SD rats were randomly assigned into shock without resuscitation group(SR group,n=24),acetated Ringer's solution resuscitation group(AR group,n=24)and ulinastatin treatment group(n=24).In all the 3 groups hemorrhagic shock models were established by femoral artery bleeding(with the mean arterial pressure maintained at 30-40 mm Hg)without resuscitation(in SR group)or with resuscitation(in AR and ulinastatin groups)using acetated Ringer's solution for 30 min at 60 min after the onset of shock.At 1,4,and 6 h after the shock onset or immediately after shock if the rats died,the lung tissues were taken for measurement of m RNA expressions of mi R-146 a,tumor necrosis factor-?(TNF-?),interleukin-1(IL-1),IL-4,IL-6 and IL-10 using real-time quantitative PCR and the protein expressions of TLR4,My D88,I?B-?,p-I?B-?,NF-?B p65,IRAK4,p-IRAK4(Thr345,Ser346),p-IRAK4(Thr342)and TRAF6 using Western blotting.The lung histopathology of the rats was examined under optical microscope with HE staining.Results:1.m RNA expression level in rat lung tissue: at 1h,there was no significant difference in IL-4 m RNA expression among the three groups(P>0.05),and at 4h and 6h,IL-1 m RNA expression in the UR group and AR There was no significant difference between the groups(P>0.05);the expressions of mi R-146 a and anti-inflammatory factors(IL-4,IL-10)in the UR group were higher than those in the AR group and the SR group at the same time point(P<0.05),AR group is higher than SR group(P <0.05).The expression of pro-inflammatory factors(such as TNF-?,IL-1,IL-6)were lower than those in AR group and SR group(P<0.05),And AR group is lower than SR group(P <0.05).2.Relative protein expression in rat lung tissue: At the same time point,the protein expression of I?B-?,p-IRAK4(Thr342)and p-IRAK4(Thr345,ser346)in UR group was higher than that in AR group and SR In group(P<0.05),AR group is higher than SR group(P <0.05).the protein expressions of TLR4,My D88,NF-?B p65,p-I?B-?,IRAK-4 and TRAF6 were lower than those in AR group and SR group(P<0.05),and AR group is lower than SR group(P <0.05).3.Lung histopathology showed that at the same time point,the lung tissue inflammation in the UR group was significantly improved compared with the AR group and the SR group,AR group is lower than SR group,mainly manifested in the structure of the alveolar cavity is clear,the pulmonary interstitial edema is reduced,and inflammatory cell exudation The degree of infiltration is also relatively light.Conclusions: 1.Sodium acetate Ringer's solution can alleviate the pathological changes of lung tissue in rats with traumatic hemorrhagic shock.The mechanism may be to increase the expression of mi R-146 a,specifically act on the targets IRAK-4 and TRAF6,and reduce I?B phosphorylation In turn,it inhibits the activation of the TLR4 /NF-?B signaling pathway,reduces the production of pro-inflammatory factors,increases the release of anti-inflammatory factors,and reverses the imbalance of inflammatory factor expression.2.Ulinastatin can further reduce lung tissue damage in rats with traumatic hemorrhagic shock on the basis of resuscitation of sodium acetate Ringer's solution,suggesting that it may play an important role in protecting important organs,providing a certain amount for further clinical research Basic and theoretical data.