Empirical Study Of RAGE Expression And Ulinastatin Intervention In Rats With Acute Respiratory Distress Syndrome Induced By Sepsis

Sepsis is still a high mortality disease,almost killing about half of the patients eventually die.Organ dysfunction,one of the most common fatal complications,often bear the brunt of the lungs.Almost half of the patients with severe sepsis were complicated with acute respiratory distress syndrome(ARDS).One important reason of the low cure rate of sepsis-induced ARDS is the unclear onset mechanism.Receptor for advanced glycation end products(RAGE)is a kind of multi-ligand receptor with many functions,having a high basal level expression in lung tissue.The main physiological role of RAGE in lung is to promote alveolar cell adhesion and assist gas exchange.However,in pathological conditions,RAGE can play an important role in the process of ARDS by starting multiple signaling pathways combined with different ligands.Ulinastatin(UTI)is a highly effective protease inhibitor with broad spectrum enzyme inhibition.Previous clinical studies have found that ulinastatin has a significant role in the treatment of ARDS caused by sepsis,but the mechanism of whether UTI intervention is effected on RAGE in ARDS has been unclear.This study is to observe the pathological injury in lung tissue,RAGE expression and ulinastatin effect on RAGE expression in rats with sepsis-induced ARDS by cecal ligation and puncture(CLP)so as to explore the regulatory effect of RAGE in ARDS and intervention messure on it.Part Ⅰ Empirical study of RAGE expression in rats with acute respiratory distress syndrome induced by sepsisObjective To observe the pathological change in lung tissue and the expression on RAGE in rats with sepsis-induced ARDS by CLP so as to explore the regulatory effect of RAGE in ARDS induced by sepsis.Methods Seventy-two Sprague-Dawley rats were randomly divided into CLP group and sham operation group.There were thirty-six rats in each group.The animal models with sepsis-induced ARDS were established by CLP in CLP group.The abdominal cavity of the rats in sham operation group was switched after anesthesia.The generally change and pathological change of the lung tissue,RAGE expressions of mRNA level and protein level in lung tissue were detected at each time point after modeling.Results The rats in CLP group analepsised later than those in sham operation group.They were depressed with unresponsive,anorexia,shortness of breath and inaction in 2 h after modeling,and the appearances became worse as time extended.The rats’ activities in sham operation group gradually returned to normal in a few hours after operation.Smith scores were higher at each time point in CLP group than those in sham operation group(all P<0.05).In CLP group,RAGE expressions of m RNA level and protein level in lung tissue were higher than which in sham operation group at 6,12,24 and 48 h after modeling(all P<0.05),reached the peak at 24 h after modeling(all P<0.05).RAGE expression of mRNA level in lung tissue was significantly associated with Smith scores at 6,12,24 and 48 h after modeling in CLP group(all P<0.01).Conclusions There were varying degrees of injures in ARDS induced by CLP,and RAGE expressions of mRNA level and protein level were increased to varying degrees,and the severity of lung issue injury was related to RAGE mRNA expression in lung issue,which indicated that RAGE might be involed in the progress of ARDS induced by sepsis.Part Ⅱ Effect of ulinastatin intervention on receptor of advanced glycation end products in rats with acute respiratory distress syndrome induced by sepsisObjective To observe the effect of ulinastatin on RAGE expressions of mRNA level and protein level in lung tissue,the concentrations of RAGE in serum and bronchoalveolar lavage fluid(BALF)in rats with sepsis-induced ARDS by CLP so as to explore the effective intervention on the mechanism of ARDS induced by sepsis.Methods One hundred and eight Sprague-Dawley rats were randomly divided into sham operation group,CLP group and ulinastatin group.There were thirty-six rats in each group.The abdominal cavity of the rats in sham operation group was switched after anesthesia and no 0.9% sodium chloride solution was injected after operation.The animal models with sepsis-induced ARDS were established by CLP in CLP group and ulinastatin group.Thirty minutes after modeling,2ml 0.9% sodium chloride solution was given every 12 h through caudal vein in CLP group and sham operation group;ulinastatin(1×105U/kg)diluted with 0.9% sodium chloride solution to 2ml was given every 12 h through caudal vein in ulinastatin group.The pathological change of the lung,RAGE expressions of mRNA level and protein level in lung tissue,and concentrations of RAGE in serum and BALF were detected at 6,12,24 and 48 h after modeling.Results Smith scores were significantly lower in ulinastatin group than those in CLP group at 12,24 and 48 h after modeling(all P<0.05).Smith scores in ulinastatin group and CLP group were significantly higher than those in sham operation group at 6,12,24 and 48 h after modeling.RAGE expressions of mRNA level and protein level in lung tissue,and the concentrations of RAGE in serum and BALF in ulinastatin group were significantly lower than those in CLP group at 6,12,24 and 48 h after modeling(all P<0.05).RAGE expressions of mRNA level and protein level in lung tissue,the concentrations of RAGE in serum and BALF were significantly higher in CLP group than those in sham operation group at 6,12,24 and 48 h after modeling(all P<0.05).Conclusions Lung issue was injured in the rats with sepsis-induced ARDS induced by CLP.RAGE expressions of mRNA level and protein level in lung tissue,concentrations of RAGE in serum and BALF were significantly decreased after intravenous injection of ulinastatin,which indicated that the protective role of ulinastatin against lung injury might be effected through inhibition of RAGE expression in ARDS induced by sepsis.