早期应用艾司洛尔对LPS诱导脓毒症大鼠心功能的影响

Early influence of esmolol on the cardiac function of LPS induced sepsis rats

目的探讨早期应用艾司洛尔对脓毒症大鼠心功能的影响。方法随机将雄性SD大鼠分为:脓毒症组(LPS组)10只,LPS建立大鼠模型,司洛尔组(ESM组)40只,LPS建立大鼠模型,按艾司洛尔不同给药时机及剂量分4个亚组:A1组;A2组;B1组;B2组以及空白组(X组)各10只。大鼠气体全麻后超声心动图法测心脏射血分数(EF%)及左室短轴缩短率(FS%);ELISA法检测血清儿茶酚胺、肌钙蛋白(TN-I)、N端脑钠肽前体(NT-pro BNP)浓度;心肌细胞匀浆提取蛋白后ELISA法检测β1、β2、β3受体亚型含量;观察心肌病理形态学改变以及电镜观察心肌线粒体超微结构的变化。结果 ESM组较LPS组在超声心动图中心脏射血分数(EF%)及左室短轴缩短率(FS%)均有改善(P<0.001);在儿茶酚胺浓度上ESM组与LPS组没有差别(P>0.05)。在TN-I及NT-pro BNP浓度上A组低于B组、A2组低于A1组(P<0.01);在β受体亚型含量上:β1受体含量A组高于B组、A2组高于A1组(P<0.01),β2受体含量各组(P>0.05),β3受体含量在ESM四亚组组间(P>0.05),但ESM四亚组较LPS组均有减少(P<0.01);免疫组化也得到结果与心肌组织ELISA法测得β受体亚型的含量的结果相一致;在心肌线粒体的超微结构观察中发现,早期应用艾司洛尔可以减轻心肌线粒体的损伤。结论对于脓毒症大鼠早期应用艾司洛尔,可以上调了心肌β1受体含量,改变β肾上腺素能受体各亚型的比例;减轻心肌线粒体的损伤,改善心肌的能量代谢,提高心功能。

Objective To explore the impacts of early application of esmolol upon cardiac functions in septic rats. Methods Male Sprague-Dawley（ SD） rats were randomly assigned into 10 rats in the sepsis group（ LPS Group） and 40 rats in the esmolol group（ ESM Group）,where rat models were constructed with LPS. Besides,they were sub-divided into four subgroups based on different medication time and doses of esmolol,including group A1,group A2,group B1 and group B2,while there were only 10 rats in the control group（ Group X）. Echocardiography measured Ejection fraction（ EF%） and left ventricular fractional shortening（ FS%） in rats were measured by echocardiography after gas anesthesia; ELISA assay was used to detect serum catecholamines,TN-I,NT-pro BNP concentration; after extraction of proteins by myocardial cell homogenates test was made of β1,β2,β3 receptor subtypes by ELISA. Changes in pathological morphology of cardiac muscle and ultramicroscopic structure of its mitochondria were observed. Results Compared with the LPS group,both the heart ejection fraction（ EF%） and the fractional shortening（ FS%） of the left ventricle were higher in the ESM group,as shown in the ultrasonic cardiogram（ P〈0. 001）,whereas there were no differences between the ESM group and the LPS group in the concentration of catecholamine（ P〉0. 05）. The concentration of TN-I and NT-pro BNP was higher in group B than those in group A and lower in group A2 than those in group A1（ P〈0. 01）. Concerning the content of β receptor subtypes,the content of β1 receptor was higher in group A than that in group B and lower in group A1 than that in group A2（ P〈0. 01）. There were no significant differences in the content of β2 receptor among all groups（ P〉0. 05） or in the content of β3 receptor between four ESM subgroups（ P〉0. 05）,whereas the content of β2 and β3 receptors decreased in four ESM subgroups compared with those in the LPS Group（ P〈0. 01）. The immunohistochemistry results were consistent with those obtained from the measurement of the content of β receptors in cardiac muscle cells by ELISA. It was observed from the ultramicroscopic structure of the myocardial mitochondria that mitochondrial damages could be reduced in the cardiac muscle with the early application of esmolol. Conclusions The early application of esmolol in septic rats could increase the content of β1 receptor in cardiac muscle,change the proportions of all β adrenergic receptor subtypes,mitigate mitochondrial damages in the cardiac muscle and improve energy metabolism in cardiac muscle cardiac functions.