脓毒性心肌病大鼠的死亡特征及机制初探  

Analysis of death characteristics and its potential mechanisms in rats with endotoxin- induced cardiomyopathy

作　　者：冯德光[1] 金春华[1] 薛翔[1] 项静[1] 

机构地区：[1]广州军区广州总医院干部病房,广东510010

出　　处：《中国危重病急救医学》2012年第12期742-746,共5页Chinese Critical Care Medicine

基　　金：国家自然科学基金项目（30570707）

摘　　要：目的探讨脓毒性心肌病大鼠的心力衰竭变化及死亡规律，以期对临床及时发现及研究脓毒性心肌病提供有意义的帮助。方法成年Wistar大鼠静脉注射精制内毒素（10mg／kg）制备内毒素血症动物模型。实验一：以自身对照，从死亡逆行观察以发现可能预测死亡的临床心功能表现；实验二：分别于注射内毒素后0（正常对照）、4、8、16、24、32、40、48、72h杀死6只大鼠，取左心室组织，行生化、常规病理、超微结构、基因表达观测，血清肌酸激酶（cK）于24h内测定，逆转录-聚合酶链反应（RT-PCR）检测a1-肌动蛋白（a-actin）基因表达。结果实验一：脓毒性心肌病大鼠心率（HR）、左室收缩期末压（LVEsP）在濒死前4h开始逐渐下降（E=22．032、Pl=0．000，F2=29．420、P2：0．000），左室内压上升／下降最大速率（±dp／dtmax）在濒死前8h开始逐渐下降（E=17．272、PI=0．000，F2=19．685、P2=0．000），直至死亡；而左室舒张期末压（LVEDP）在整个过程中未出现显著变化（F=0．265，P=0．988）。注射内毒素4h内大鼠未见显著的心功能变化，24h内死亡率73．9％，大部分死于注射后8—16h，一旦存活超过24h的个体就有2／3的机会存活超过48h。实验二：24h内内毒素各组间CK差异无统计学意义（F-=0．402，P=0．805），但表现出很大的离散性。光镜及电镜结果显示，注射内毒素8h后，心肌细胞间及细胞内出现明确损害，光镜下可见心肌细胞排列混乱，毛细血管出血，心肌横纹消失，线粒体肿胀、消失，心肌力学构架破坏，心肌侧向分离；电镜下可见心肌细胞内纤维走向及横纹消失，线粒体损伤，纤维破坏，细胞问的连接受损严重。与正常对照组（0．6374-0．160）比较，注射内毒素后基因表达逐渐下降，8h达谷底（0．493±0．067），然后逐渐上升，32h达到第二个低谷（0．875±0.128），但[Abstract] Objective To approach the changes in heart failure and dying regularity of rats with endotoxin-induced cardiomyopathy, and to offer some help for clinical diagnosing and further investigation. Methods Injecting refined endotoxin （ 10 mg/kg） via vein of Wistar rats. The first experiment： antidromic observing the endotoxic rats from death to the beginning to discover the performance of clinic heart function which could forecast death. The second experiment： setting 6 rats per group, respectively killing the rats at 4, 8, 16, 24, 32, 40, 48 and 72 hours after endotoxin injection, and killing 6 normal rats as control group, getting the tissue of left ventricle for biochemistry test, routine pathological examination, transmission electron microscope examination, expression level of cq-actin gene with reverse transcription-polymerase chain reaction （RT-PCR）, and serum creatine kinase （CK） was test within 24 hours. Results The first experiment： heart rate （HR） and left ventricular end-systolic pressure （LVESP） of endotoxic rats began significant lower than normal at 4 hours before death （F1=22.032, PI=0.000; F2=29.420, P2= 0.000）, maximum rate of rise/drop of left ventricular pressure （ ± dp/dt max） began significant lower than normal at 8 hours before death （F1=17.272, P,=0.000; F2=19.685, P2=0.000）, left ventricular end-diastolic pressure （LVEDP） showed no significant during the whole time （F= 0.265, P= 0.988 ）. The heart function of all the rats showed no significant changes in the first 4 hours after injection. Mortality was 73.9% from injection to 24 hours later. Most of them died in 8-16 hours after injection. The one who had survived over 24 hours ould have 2/3 probability to survive to 48 hours. The second experiment： CK in serum of different groups showed no significant difference （F=0.402, P= 0.805）, but showed obvious discreteness in each group except normal group. Electron microscopy and pathological examination showed obvious intracellular and

关 键 词：内毒素 脓毒性心肌病 心力衰竭 肌动蛋白 

分 类 号：R459.7[医药卫生—急诊医学]