左西孟旦对脓毒症心肌损伤小鼠的保护作用及机制研究  

Protective effect and mechanism of Levosimendan on sepsis induced myocardial injury in mice

作　　者：柴鹏程 韩海波 胡振杰[2] 陈玉红[2] CHAI Peng-cheng;HAN Hai-bo;HU Zhen-jie;CHEN Yu-hong(Clinical College,Hebei Medical University,Shijiazhuang 050020,China;Department of critical care medicine,The Fourth Hospital,Hebei Medical University,Shijiazhuang 050011,China)

机构地区：[1]河北医科大学临床学院,石家庄050020 [2]河北医科大学第四医院重症医学科,石家庄050011

出　　处：《天津医科大学学报》2023年第5期481-485,513,共6页Journal of Tianjin Medical University

基　　金：河北省高等学校大学生创新创业训练项目(S202113415013)。

摘　　要：目的:探讨左西孟旦(Levo)对脓毒症心肌损伤(SMI)小鼠心脏功能的保护作用及其作用机制。方法:清洁级雄性C57小鼠,体重25~30 g,适应性饲养1周,腹腔注射脂多糖(LPS)复制SMI疾病模型。将小鼠随机分为正常对照(Control)组、SMI组、SMI+Levo组,共3组(n=6)。心脏超声观察小鼠左室射血分数(LVEF)、左室缩短分数(LVFS)及心输出量(CO)变化,并留取小鼠静脉血和心脏组织,酶联免疫吸附法(ELISA)测定血浆肌钙蛋白Ⅰ(cTnI)、肌酸激酶(CK)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)水平,苏木精-伊红染色(HE)观察心脏形态学改变,电镜观察心肌组织线粒体形态及自噬小体。结果:与Control组相比,SMI组的LVEF、LVFS及CO明显下降(分别为65.96±8.16 vs.35.78±4.87,35.87±6.05 vs.16.80±2.58,18.19±2.84 vs.9.34±1.23,均P<0.01),血浆cTnI(ng/mL)、CK(U/L)、TNF-α(μg/L)、IL-1β(μg/L)水平明显升高(分别为1.25±0.36 vs.6.99±0.39,866.93±378.51 vs.5427.22±875.23,58.33±10.98 vs.658.50±91.87,32.83±3.43 vs.114.83±5.98,均P<0.01)。与SMI组比较,SMI+Levo组的LVEF、LVFS及CO均明显升高(分别为35.78±4.87 vs.45.88±2.63,16.80±2.58 vs.24.01±3.4,9.34±1.23 vs.14.80±3.41,均P<0.01),血浆cTnI、CK、TNF-α、IL-1β水平明显下降(分别为6.99±0.39 vs.6.24±0.46,5427.22±875.23 vs.3587.67±460.90,658.50±91.87 vs.431.00±18.17,114.83±5.98 vs.74.70±26.13,均P<0.01)。光镜下Control组心肌形态学结构正常;SMI组可见心肌纤维变性,炎细胞浸润等改变;SMI+Levo组上述改变可见明显好转。电镜下可见Control组心肌细胞形态正常,心肌纤维排列整齐,线粒体形态规整;SMI组心肌细胞可出现坏死改变,心肌纤维排列不整齐,线粒体排列紊乱,水肿,自噬小体增多;SMI+Levo组上述病理改变有明显好转。结论:Levo对SMI小鼠具有心脏保护作用,其机制可能是通过减轻炎症反应、改善线粒体功能发挥作用。Objective:To investigate the protective effect of Levosimendan(Levo)on cardiac function in septic myocardial injury(SMI)mice and its mechanism.Methods:Clean grade male C57 mice,weighing 25-30 g,were fed adaptively for one week,and intraperitoneal injection of lipopolysaccharide(LPS)was used to make sepsis myocardial injury disease model.The mice were randomly divided into three groups(n=6):control group,SMI group,and SMI+Levo group.The changes of left ventricular ejection fractions(LVEF),left ventricular fractional shortening(LVFS)and cardiac output(CO)in mice were observed by echocardiography,and venous blood and cardiac tissue were collected.Plasma cardiac troponin I(cTnI),creatine kinase(CK)and tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)were measured by enzyme-linked immunosorbent assay(ELISA).Hematoxylin eosin staining(HE)was used to observe the morphological changes of the heart,and electron microscopy was used to observe the morphology of myocardial mitochondria and autophagosomes.Results:Compared with the control group,LVEF,LVFS and CO in SMI group decreased significantly(65.96±8.16 vs.35.78±4.87,35.87±6.05 vs.16.80±2.58,18.19±2.84 vs.9.34±1.23,respectively,all P<0.01).Plasma cTnI(ng/mL),CK(U/L),TNF-α(μg/L)、IL-1β(μg/L)level increased significantly(1.25±0.36 vs.6.99±0.39,866.93±378.51 vs.5427.22±875.23,58.33±10.98 vs.658.50±91.87,32.83±3.43 vs.114.83±5.98,respectively,all P<0.01).Compared with SMI group,LVEF,LVFS and CO in SMI+Levo group increased significantly(35.78±4.87 vs.45.88±2.63,16.80±2.58 vs.24.01±3.4,9.34±1.23 vs.14.80±3.41,respectively,all P<0.01),plasma level of cTnI,CK,TNF-α,IL-1βwere significantly decreased(6.99±0.39 vs.6.24±0.46,5427.22±875.23 vs.3587.67±460.90,658.50±91.87 vs.431.00±18.17,114.83±5.98 vs.74.70±26.13,respectively,all P<0.01).Myocardial morphology was normal in control group under light microscope.Myocardial fibrosis and inflammatory cell infiltration were observed in SMI group.In SMI+Levo group,the above changes were obviously im

关 键 词：脓毒症 脓毒症心肌损伤 左西孟旦 心脏 线粒体 

分 类 号：R961[医药卫生—药理学]