β受体拮抗剂对脓毒症大鼠心肌细胞线粒体损伤的保护作用

Protective Effect of a β-Receptor Antagonist on the Impairment of Cardiocyte Mitochondria in a Rat Sepsis Model

目的探讨β受体拮抗剂对脓毒症大鼠心肌细胞线粒体功能的影响。方法取SD大鼠20只,随机分为4组,每组5只。对照组不做处理,剩余3组采用小剂量内毒素持续注射法建立脓毒症大鼠模型,并分为模型组,美托洛尔组和艾司洛尔组。治疗前(0 h)、治疗24 h和48 h后检测各组大鼠心率、平均动脉血压;并于治疗48 h后处死大鼠,取心肌组织切片行病理学检测:HE染色,电子显微镜下观察线粒体;qPCR和Western blotting检测各组线粒体内膜特异的腺甘酸转移酶(ANT) mRNA和蛋白表达水平。结果内霉素建模后,模型组、美托洛尔组和艾司洛尔组大鼠与对照组比较均出现精神萎靡不振、竖毛、嗜睡、眼鼻渗血、稀便等脓毒症症状,体温和白细胞均显著下降(均P <0.001),而血清TNF-α及IL-6表达水平均显著升高(均P <0.05),表明脓毒症大鼠模型建立成功。治疗48 h后,美托洛尔组和艾司洛尔组心率低于模型组,而平均动脉压高于模型组(均P <0.05)。模型组大鼠心肌细胞排列疏松,电镜下细胞肌纤维断裂,线粒体、肌浆网形态辨认困难,而美托洛尔组和艾司洛尔组大鼠心肌细胞形态接近对照组,电子显微镜下可见心肌细胞肌纤维束排列有序,线粒体、肌浆网形态可见但有部分异常。美托洛尔组和艾司洛尔组ANT mRNA和蛋白表达水平均显著高于模型组(均P <0.05)。结论β受体拮抗剂对脓毒症心肌细胞线粒体损伤具有一定保护作用。

Objective To investigate the protective effect of a β-receptor antagonist on the impairment of cardiocyte mitochondria in a rat sepsis model.Methods Twenty SD rats were randomized into control,model,metoprolol,and esmolol groups.Continuous lipopolysaccharide(LPS)injection was used to establish a rat sepsis models.Heart rate(HR),mean arterial pressure(MAP),and mitochondrial-specific expression of adenosine transferase(ANT)were measured.Mitochondrial morphology was observed by hematoxylin and eosin staining.Results After LPS stimulation,rats in the model,metoprolol,and esmolol groups presented with sepsis symptoms,decreased body temperature and white blood cell counts,and increased serum tumor necrosis factor-αand interleukin-6 expression compared with those in the control group(all P<0.05).After treatment for 48 h,HR decreased,while MAP increased in metoprolol and esmolol groups relative to those in the model group(all P<0.05).Rats in the model group showed loosely arranged cardiocytes,and abnormal unrecognized mitochondria and sarcoplasmic pattern under the microscope.In contrast,rats in the metoprolol and esmolol groups showed orderly aligned cardiocytes,and recognizable but still abnormal mitochondria and sarcoplasmic pattern.In addition,ANT mRNA and protein expression were both elevated in the metoprolol and esmolol groups compared to those in the model group(all P<0.05).Conclusionβ-receptor antagonists had a protective effect on the impairment of cardiocyte mitochondria in a rat sepsis model to some extent.