Effects Of Early Use Of Esmolol On Cardiomyocyte Apoptosis And Oxidative Stress In Septic Rats

Objective To observe the effects of the early use of esmolol on myocardial oxidative stress,expression of apoptosis-related proteins,mitochondrial structure and cardiac function in septic rats,and explore its mechanism in cardioprotectionMethods 63 male Wistar rats were divided into a sham operation group(Sham group),a sepsis group(CLP group),and an esmolol group(ES group).Each group was divided into 6 hour,12 hour,and 24 hour subgroups.The Sham group underwent sham surgery only.Both the CLP and ES groups used cecal ligation and puncture(CLP)method to establish rat sepsis model.The Sham group and the CLP group were continuously infused with 0.9% sodium chloride solution at a speed of 1ml/h by micropump for 6h,while the ES group was continuously infused with esmolol diluted solution [15 mg/kg/h] at a speed of 1ml/h for a total of 6h.The rats were sacrificed at the time points of 6 h,12 h and 24 h after the administration of the drug.Open the chest quickly under aseptic conditions,collect blood and extract the heart,and then freeze the serum and heart tissue samples.Serum TNF-? and BNP levels were measured by ELISA.The WST-1 method for detecting SOD activity in rat myocardial tissue was used.Spectrophotometry was used to determine tissue MDA content in myocardial tissue.The expression levels of caspase-3,bcl-2,Bax and other proteins in myocardial tissue were detected by Western Blot.Observe the morphology and structure of myocardial mitochondria under electron microscope.Results 1.Serum TNF-?: At 6h,12 h,and 24 h after surgery,serum TNF-? levels in the CLP and ES groups were significantly higher than those in the Sham group,and the difference was statistically significant(P <0.05).The TNF-? levels in the ES group were significantly lower than those in the CLP group at each time point(P<0.05).2.Oxidative stress level: At 6h,12 h,and 24 h after surgery,myocardial SODactivity in the CLP and ES groups was significantly reduced,and the difference was statistically significant compared with the Sham group(P <0.05).The SOD activity of ES group was significantly higher than that of CLP group at each time point(P <0.05).At 6h,12 h,and 24 h after surgery,the MDA content in CLP and ES tissues increased significantly,and the difference was statistically significant compared with the Sham group(P <0.05).At 6h,12 h,and 24 h after surgery,the MDA content in ES tissues reduced significantly,and the difference was statistically significant compared with the Sham group(P <0.05).3.Apoptotic/antiapoptotic protein: At 6h,12 h and 24 h after operation,the expression of Caspase-3 and Bax in the CLP and ES groups was significantly higher than that in the Sham group,and the difference was statistically significant(P <0.05).The expression of Caspase-3 and Bax in the ES group was significantly lower than that in the CLP group,the difference was statistically significant(P <0.05).At 6h,12 h and 24 h after surgery,the expression of Bcl-2 in the CLP and ES groups was significantly lower than that in the Sham group,and the difference was statistically significant(P <0.05),and the expression of Bcl-2 in the ES group was significantly higher than that in the CLP group,the difference was statistically significant(P<0.05).4.Serum BNP levels: At 6h,12 h,and 24 h after surgery,serum BNP levels in the CLP and ES groups were significantly higher than those in the Sham group.The difference was statistically significant(P <0.05).The BNP level in the ES group was significantly lower than that in the CLP group at 6h and 12 h after surgery,the difference was statistically significant(P <0.05).At 24 hours after surgery,the BNP level in the ES group was not significantly different from that in the CLP group(P >0.05).5.Under the electron microscope,myocardial fibers and mitochondria were almost intact in the Sham group,and there was no significant difference at each time point.The degree of damage was the most severe in the CLP group,and the degree of damage gradually increased with time,while the myocardial fibers and mitochondria of the ES group at each time point were alleviated compared with the time points of the CLP group.Conclusions Early application of esmolol can reduce the production of TNF-?in serum,decrease myocardial Bax and Caspase-3 expression,increase Bcl-2expression,reduce oxidative stress response,protect myocardial mitochondrial structure and reduce serum BNP level.The preliminary mechanism may be that esmolol may inhibit the endogenous and exogenous pathways of apoptosis by reducing the production of the apoptosis initiation factor TNF-?.While inhibiting apoptosis,it reduces the oxidative stress response,which is both the accompanying process of apoptosis and an important initiator of apoptosis.It also can protect the mitochondrial structure of target organelles damaged by apoptosis and oxidative stress.