Inhibitory effects of intensive insulin on myocardium expression of tumor necrosis factor alpha in severely burnt rats / 解放军医学杂志

ABSTRACT

Objective To investigate the inhibitory effects of intensive insulin on myocardium expression of tumor necrosis factor alpha(TNF-?)in severely burnt rats and its correlative mechanism.Methods In eighteen SD rats the right jugular vein and the left ventricle were cathetetized,and were divided into three groups randomly(1)the sham burn group,the rats were treated by sham burn;(2)the burn group,the rats were inflicted with 30%TBSA Ⅲ degree burn,and then given fluid resuscitation routinely;(3)the intensive insulin group,the rats received intensive insulin treatment after burn,and the liquid volume given was equal to the burn group.The level of plasma glucose contents,the left ventricular systolic pressure(LVSP)and left ventricular end-diastolic pressure(LVEDP)were recorded at 1,2,3,4,5,6h after burn,and animals were sacrificed at 6 hours after burn.The level of TNF-? in myocardium tissue was assayed by ELISA,and mRNA expression was determined by real-time PCR.Western blot was used to detect I?B? phosphorylation and degradation in left ventricle tissue.Meanwhile,burn serum-challenged cardiomyocytes were also used to detect the levels of insulin and LY294002,a specific insulin activation inhibitor,on the phosphorylation of I?B?.Results The animals showed stress hyperglycemia after burns,the function of heart was damaged(LVSP degraded and LVEDP increased),the level of TNF and the expression of mRNA in the myocardium increased apparently,I?B? phosphorylation and degradation increased in left ventricle tissue and burn serum-challenged cardiomyocytes.Given the intensive insulin treatment to keep the blood glucose level between 4.5 to 5.2 mmol/L,the function of heart was significantly improved,the level of TNF-? was apparently lowered,and the I?B? phosphorylation and degradation were significantly decreased.LY294002 could abolish the inhibitory effect of insulin,and it acted on the I?B? phosphorylation on burn serum-challenged cardiomyocytes model.Conclusion Intensive insulin may decrease the activation of NF-?B through diminishing the I?B? phosphorylation and degradation,which inhibit the transcription and expression of TNF-? in myocardial cell,and improve the heart function accordingly.