摘要
目的研究无创性延迟肢体缺血预适应(NDLIP)对心脏猝死的预防作用。方法取健康,体质量(250±10)g的SD♂大鼠30只,随机分为3组,1心肌梗死(MI)组:手术结扎动物冠状动脉左前降支(left anterior descending artery,LAD),2周后成模;2 MI+NDLIP组:动物心肌梗死模型成功后,每隔1 d进行1次远端肢体缺血预适应,直至第4周;3假手术(Sham)组:作为阴性对照组,心脏LAD只穿线不结扎,不实施NDLIP。各组动物常规饲养,于4周末静脉输注间羟胺(0.2 mg·min^(-1))进行猝死,记录致猝死过程中的ECG、猝死药物累积量、猝死时间,于猝死末期腹主动脉取血,ELISA法测定血清caspase-3、HSP70、SOD含量。结果间羟胺致动物心脏猝死时,随着给药量的增加,动物的心率呈下降趋势,记录给药0、5、10、30、50、70、90 min时动物的心率。与MI组相比,MI+NDLIP组给药0、5、10、30、50 min时动物心率[(479±8)vs(416±19)beat·min^(-1),(446±32)vs(370±20)beat·min^(-1),(376±53)vs(305±29)beat·min^(-1),(307±63)vs(244±33)beat·min^(-1),(283±45)vs(121±35)beat·min^(-1),P<0.01]明显较高。与MI组相比,MI+NDLIP组动物的致猝死药物累积量、猝死时间[(14.58±3.03)vs(10.76±2.73)mg,(72.9±15.2)vs(53.8±13.6)min,P<0.01]都明显增加。与MI组相比,MI+NDLIP组血清caspase-3[(2.01±0.52)vs(2.34±0.38)μg·L^(-1),P<0.01]表达量明显降低;HSP70[(3.01±0.58)vs(2.70±0.43)μg·L^(-1),P<0.05]水平明显升高;SOD[(1.99±0.65)vs(1.70±0.58)mg·L^(-1),P<0.01]水平明显升高。结论无创性延迟肢体缺血预适应能有效预防大鼠心梗后心脏性猝死,其机制可能与降低心肌细胞凋亡、增加保护性蛋白的表达以及增强心肌抗氧化能力有关。
Aim To study the preventative effects of noninvasive delayed limb ischemic preconditioning( NDLIP) on sudden cardiac death in rats with myocardial infarction. Methods Thirty healthy SD male rats weighting( 250 ± 10) g were randomly divided into 3groups: 1 myocardial infarction( MI) group: animal model of MI was established by making surgical ligation of animal LAD. 2 MI plus NDLIP group: after the success of the animal model of MI,NDLIP was carried out every other day until 4th week. 3 Sham group: as the negative control group,animals were taken heart LAD threading but no ligation. All rats were fed conventionally. At the end of 4 weeks,three groups of rats were administered with metaraminol( 0. 2 mg ·min^(-1)). ECG,drug cumulant of sudden death and death onset time were recorded. After sudden death,blood samples were withdrawn from abdominal aorta and serum was separated via centrifugation. ELISA method was used to measure serum caspase-3,HSP70 and SOD concentration. Results While metaraminol led animal cardiac sudden death,the rats heart rate( HR) kept declining with the increase of dosage of metaraminol during the administration period. Rat HR of MI + NDLIP group [( 479 ± 8) vs( 416 ± 19) beat·min^(-1),( 446 ± 32) vs( 370 ± 20) beat·min^(-1),( 376 ± 53) vs( 305 ± 29) beat·min^(-1),( 307 ± 63)vs( 244 ± 33) beat · min^(-1),( 283 ± 45) vs( 121 ±35) beat · min^(-1),P < 0. 01] was markedly higher than that of MI group at 0,5,10,30,50 min before death. Compared with MI group,drugs cumulant to sudden death and death onset time of MI + NDLIP group [( 14. 58 ± 3. 03) vs( 10. 76 ± 2. 73) mg,( 72. 9 ± 15. 2) vs( 53. 8 ± 13. 6) min,P < 0. 01]were significantly increased. Compared with MI group,serum caspase-3 content of MI + NDLIP group was significantly reduced [( 2. 01 ± 0. 52) vs( 2. 34 ± 0. 38)μg·L^(-1),P < 0. 01]; HSP70 levels were remarkably increased [( 3. 01 ± 0. 58) vs( 2. 70 ± 0. 43) μg ·L^(-1),P < 0. 05]; SOD levels were significantly improved [( 1. 99 ± 0. 65) vs( 1. 70 ± 0. 58)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2016年第11期1565-1570,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81072631)
天津自然科学基金资助项目(No 09JCZDJC21100)
