Study For Insulin In Protection Against LPS-induced Acute Lung Injury In Rats

Objective:To explore the changes of nuclear factor kappa B(NF-κB)and intercellular adhesion molecule-1(ICAM-1)as well as the level of oxidation/anti-oxidation in LPS-induced acute lung injury in rats.And to investigate the mechanisms of insulin in the prevention in LPS-induced acute lung injury(ALI).Methods:24 SD rats(190-210g)were anesthetized,and divided randomly into three groups: physiologic saline control group,LPS group,insulin +LPS group(Plasma glucose was clamped at the level of the two other groups by infusion of 10%glucose solution.).A femoral vein was used for intravenous administration of fluid.The rats in control group were subjected to physiologic saline for 125 mins;Lipopolysaccharide was administered intravenously 5 mins after saline infusion in LPS group,and physiologic salina was continued for 125 mins.While insulin and glucose infusion was started 5 mins before lipopolysaccharide and continued for 125 mins in insuin+LPS group.(All the fluid was given at the rate of 0.01 ml/min.)At the termination of the study,all the animals were executed after the blood glucose determination.The Histopathologic changes of lung were examined under a light microscope,and the expression of NF-κB and ICAM-1 were determined by immunohistochemistry.MDA and SOD were also detected in order to evaluate the oxidation/anti-oxidation of ALI.Results:1.LPS group showed histopathologic changes of ALI:Lung histopathologic changes following LPS included alveolar edema,airway congestion,widening of the interstitium,and reaction cell infiltration.Insulin reduced these LPS-induced changes.2.Compared with the control group,LPS group had more activity in NF-κB and insulin had the capability to inhibit the process.The average optical density values were:0.308±0.017, 0.542±0.009,0.427±0.018,the differences between any two groups were significant at 0.05 level. ICAM-1 was expressed in vascular endothelial cells in control group,LPS up-regulated the expression of ICAM-1 while insulin played an opposite role.The average optical density values were:0.274±0.014,0.456±0.018,0.357±0.024,there were statistical significances between any two groups(P＜0.05).3.The content of MDA in the lung tissue homogenate in LPS group was 2.656±0.088 nmol/mgprot,which was much higher than that in control group—only 1.556±0.069 nmol/mgprot,and insulin reduced the change to 1.948±0.127 nmol/mgprot.As to the SOD,the values were as follows:control group,80.999±3.241U/mgprot;LPS group, 55.812±2.939U/mgprot;LPS+insulin group,63.472±2.835U/mgprot.Both of the indexes had significant differences between any two groups(P＜0.05).Conclusions:1.ALI animal models were performed by LPS intravenous administration,and it was confirmed that the model was successful.2.LPS had the abilities to active NF-κB,make more expression of ICAM-1 and bring about generous free radicals to make oxidative damage in the lung,while the anti-oxidation was descended.3.The results of the present study suggested that insulin had anti-inflammatory and anti-oxidation effects including an inhibition of the activities of NF-κB and the expression of ICAM-1,a decrease in MDA,and an increase in SOD.The study revealed that insulin infusion significantly reduced the LPS-induced ALI,and showed its protection for the lung in LPS-induced acute lung injury in rats.