SR9009对内毒素血症小鼠心肌损伤的影响  

Effect of SR9009 on myocardial injury in endotoxemic mice

作　　者：李璐[1] 邱珍[1] 田浩 雷少青[1] 夏中元[1] Li Lu;Qiu Zhen;Tian Hao;Lei Shaoqing;Xia Zhongyuan(Department of Anesthesiology,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院麻醉科,武汉430060

出　　处：《中华麻醉学杂志》2023年第3期346-349,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(81970722);中央高校基本科研业务费专项资金资助(2042021kf0113)。

摘　　要：目的评价SR9009对内毒素血症小鼠心肌损伤的影响。方法SPF级健康雄性C57BL/6小鼠18只,5周龄,体质量21~24 g,采用随机数字表法分为3组(n=6):对照组(C组)、内毒素血症组(LPS组)和内毒素血症+SR9009组(LPS+SR组)。LPS+SR组于下午4点腹腔注射SR900950 mg/kg;LPS组于第2天上午10点腹腔注射LPS 15 mg/kg制备小鼠内毒素血症模型。LPS注射后9 h,行超声心动图检测左室功能;直视下心腔取血,采用ELISA法检测血清CK-MB、LDH和cTnI水平;取心肌组织,HE染色后,光镜下观察病理学结果;采用Western blot法检测心肌组织Beclin1、P62和微管相关蛋白1轻链3(LC3)的表达,计算LC3Ⅱ/LC3Ⅰ比值。结果与C组相比,LPS组射血分数和短轴收缩率降低,左心室舒张末期内径和左心室收缩末期内径缩短,左心室舒张末期后壁厚度和左心室收缩末期后壁厚度减小,血清CK-MB、LDH和cTnI水平升高,心肌组织P62表达下调,Beclin1表达上调,LC3Ⅱ/LC3Ⅰ比值升高(P<0.05),心肌组织发生病理学损伤。与LPS组相比,LPS+SR组射血分数和短轴收缩率升高,左心室收缩末期内径缩短,左心室舒张末期后壁厚度减小(P<0.05),左心室舒张末期内径和左心室收缩末期后壁厚度差异无统计学意义(P>0.05),血清CK-MB、LDH和cTnI水平降低,心肌组织P62表达上调,Beclin1表达下调,LC3Ⅱ/LC3Ⅰ比值降低(P<0.05),心肌组织病理学损伤减轻。结论SR9009可减轻内毒素血症小鼠心肌损伤,其机制可能与抑制自噬有关。Objective To evaluate the effect of SR9009 on myocardial injury in endotoxemic mice.Methods Eighteen SPF healthy male C57BL/6 mice,aged 5 weeks,weighing 21-24 g,were divided into 3 groups(n=6 each)by the random number table method:control group(C group),endotoxemia group(lipopolysaccharide[LPS]group)and endotoxemia+SR9009 group(LPS+SR group).SR900950 mg/kg was intraperitoneally injected at 4:00 p.m.in LPS+SR group.The endotoxemic model was prepared by intraperitoneal injection of LPS 15 mg/kg at 10 a.m.on the second day in mice.The left ventricular function was monitored by echocardiography at 9 h after LPS injection.Blood samples were collected from the heart cavity under direct visualization for determination of the serum creatine kinase isoenzymes(CK-MB),lactic dehydrogenase(LDH)and cardiac troponin I(cTnI)levels by enzyme-linked immunosorbent assay.Myocardial tissues were obtained and stained with HE for microscopic examination of the pathological changes(with a light microscope)and for determination of the expression of Beclin1,P62 and microtubule-associated protein 1 light cain 3(LC3)(by Western blot),and the ratio of LC3Ⅱto LC3Ⅰwas calculated.Results Compared with group C,the ejection fraction and short-axis fractional shortening were significantly decreased,the left ventricular end-diastolic internal diameter and left ventricular end-systolic internal diameter were shortened,the left ventricular end-diastolic posterior wall thickness and left ventricular end-systolic posterior wall thickness were decreased,serum CK-MB,LDH and cTnI levels were increased,P62 expression in myocardial tissues was down-regulated,Beclin1 expression was up-regulated,LC3Ⅱ/LC3Ⅰratio was increased(P<0.05),and the pathological changes were found in myocardial tissues in group LPS.Compared with group LPS,the ejection fraction and short-axis fractional shortening were significantly increased,the left ventricular end-systolic internal diameter was shortened,and the left ventricular end-diastolic posterior wall thickness was dec

关 键 词：内毒素血症 心肌损伤 SR9009 

分 类 号：R614[医药卫生—麻醉学]