| Objective In order to study whether Esmolol can protect the heart by inhibiting the classical pathway of pyroptosis.Methods Seventy two male rats(250-300g)were randomly divided into Sham group(sham operation + 0.9% sodium chloride solution),CLP group(CLP +0.9% sodium chloride solution)and ES group(CLP + Esmolol),24 rats in each group.The three groups were further divided into two subgroups A and B,8 rats in group A were assigned to observe the survival days;group B was the experimental group,and each group was further divided into 6h and 24 h groups according to the postoperative treatment time,eight rats were randomly assigned at each time point.The Sham group was only given the treatment of laparotomy and turning cecum,and the abdomen was disinfected and closed after the treatment.CLP group and ES group used cecal ligation puncture method to establish sepsis rat model.The rats in Sham group and CLP group were continuously pumped with 0.9% sodium chloride solution through the left internal jugular vein for 6h(1ml/h).In ES group,Esmolol was pumped into the left internal jugular vein at a rate of 15 mg/kg/h for 6 h(1 ml/h),and then the rats were executed at the corresponding time points(6h and 24 h after the completion of the drug pumping)and the samples were obtained.The levels of IL-1 β and IL-18 in serum were detected by ELISA,and western blot methods detected the expression levels of NLRP3,Caspase-1 and GSDMD protein in myocardial tissue,the pathological changes of myocardial tissue were observed under light microscope.Tunel staining and DAPI staining were used to observe the myocardial cell death under fluorescence microscope,and the survival time array was used to observe and analyze the survival status.Results(1)The results of ELISA showed that compared with Sham group at each time point,the levels of IL-1βand IL-18 in serum of ES group were significantly increased,especially at 24h;compared with CLP Group,the levels of these factors were significantly decreased at 6 h and 24 h(P<0.05).(2)Western blot showed that the expression of classical pathway related proteins of pyroptosis of NLRP3,Caspase-1 and GSDMD in CLP group was significantly higher than that in Sham group(P < 0.05),and the highest expression was 24 h after operation.The expression of these proteins in ES group was lower than that in CLP Group at each time point,and the difference was statistically significant.(3)The pathological results showed that the myocardial tissue of Sham group showed slight pathological damage,and the myocardial cell damage of CLP group was the most serious.The myocardial cell damage of ES group was significantly less than that of CLP group,and the 24 h group damage degree of each group was heavier than that of 6h group.(4)At 24 h group,Tunel and DAPI staining showed that compared with a small number of positive cells in Sham group,a large number of positive cells were observed in CLP group,and the difference was statistically significant.Compared with CLP group,the number of positive staining cells in ES group was significantly reduced(P < 0.05).(5)The 7day survival analysis showed that the mortality of CLP group was the highest,and the survival days of ES group were significantly longer than that of CLP group(P < 0.01).Conclusions Esmolol can inhibit the occurrence of pyroptosis,alleviate myocardial injury and improve the survival rate of septic rats.The mechanism may be related to the inhibition of NLRP3,Caspase-1,GSDMD protein expression and the reduction of inflammatory factor release. |
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