The Cardioprotective Effects Of Esmolol In Septic Rats And Its Possible Mechanism

Objective:By observing the effect of esmolol on the survival,myocardial pathology,myocardial enzymes and inflammatory mediators in septic rats,and detecting the activation of TLR4/Myd8/NF-?B signaling pathway,and then exploring the myocardial protective effect and possible mechanism of esmolol in septic rats,providing experimental basis for the treatment of septic cardiomyopathy with esmolol.Methods:Sixty male clean SD rats were selected as the research object and randomly divided into three groups by random number method: sham operation group(Sham group,Sham group),sepsis group(Model group,Model group)and esmolol group(Esmolol group,ES group)with 20 rats in each group.Sham group was treated with cecum exploration,Model group and ES group were treated with cecal ligation and perforation(CLP method)to establish septic rat model.After operation,ES group continuously pumped esmolol diluent 1 ml/h [15mg·kg-1·h-1] for 6 hours.Sham group and Model group pumped 1ml/h of normal saline for a total of 6 hours.The survival condition of rats in each group was observed 24 hours after operation.Abdominal aortic blood was taken to detect the expression levels of troponin I(TnI),tumor necrosis factor ?(TNF-?),interleukin-1(IL-1).The free wall of the left ventricle was taken for HE staining to observe the pathological changes of myocardium.The contents of Toll-like receptor-4(Toll-like receptor-4,TLR4),myeloid differentiation protein 88(Myeloid differentiation factor-88,Myd 88)and nuclear factor-? B(Nuclear factor-kappa B,NF-?B)were detected by Western blot method.Results:(1)The changes of survival conditions in rats of each group: 6h after the operation of Model,rats in Model group showed decreased activity,listlessness,hair erection and chills.12 h after the operation,the rats had lethargy,withered hair,curled up in the corner of the cage,had little activity,and the intake of water and food plummeted.Sham group of rats had good wound healing,white and lustrous fur,good mobility and normal eating.The state of rats in ES group is better than that in Model group,and their mobility is acceptable,but it is worse than that in Sham group.The survival rate was 90.0% for 2 deaths in the Sham group,55.0% for 9 deaths in the Model group and 65.0% for 7 deaths in the ES group.There was no significant difference in survival rate between ES group and CLP group(P > 0.05).(2)The changes of myocardial pathology in rats of each group: Under light microscope,myocardial cells in Sham group were normal in structure,fiber bundles were closely arranged,and no obvious edema,hyperemia,degeneration and necrosis were found in cells.In Model group,myocardial cells showed massive necrosis,vacuolar degeneration,obvious edema of myocardial fibers,loose arrangement,partial rupture of myocardial fibers,swelling of nucleus,interstitial edema and inflammatory cell infiltration.ES group compared with Model group,myocardial cells showed less necrosis,irregular arrangement of myocardial fibers,no obvious edema in stroma,and a small amount of inflammatory cell infiltration.Myocardial histopathological score showed that Model group>ES group>Sham group(p<0.05).(3)The changes of myocardial enzymes in rats of each group: the contents of TnI in serum of rats in Model group was significantly higher than that in Sham group,while the contents of TnI in serum of ES group was significantly lower than that in Model group(p<0.05).(4)The changes of inflammatory mediators in rats of each group:the contents of TNF-? and IL-1 in serum of rats in Model group were significantly higher than those in Sham group,while the contents of TNF-? and IL-1 in serum of ES group were significantly lower than those in Model group(p < 0.05).(5)The changes of TLR4,MyD88 and NF-?B protein expressions in myocardial tissues of rats in each group:Western blot analysis showed that the expression of TLR4,Myd88 and NF-? B protein in Model group was significantly higher than that in Sham group(p < 0.05).Compared with Model group,the expression of TLR4,Myd88 and NF-?B protein in ES group was significantly lower than that in ES group(p < 0.05).Conclusion:Esmolol can reduce the release of inflammatory factors in septic rats,improve inflammatory response and relieve myocardial injury,and thus play a protective role in myocardium.Its mechanism may be related to inhibition of activation of TLR4/MyD88/NF-?B signaling pathway.