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衰老大鼠心肌对缺血再灌注损伤的敏感性研究 被引量:4

The study of susceptibility to ischemia-reperfusion injury in heart of aged rat
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摘要 目的观察衰老大鼠心肌对缺血再灌注损伤的敏感性,并探讨其可能的机制。方法成年和老年雄性Wistar大鼠各12只,分为4组:成年假手术组、成年缺血再灌注组、老年假手术组和老年缺血再灌注组,每组6只,进行缺血30 min再灌注3 h。脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)法检测心肌细胞凋亡,比色法检测心肌组织半胱胺酸蛋白酶蛋白-3 (caspase-3)活性,化学发光法测定心肌组织总一氧化氮(NOx)含量,ELISA法检测心肌过氧亚硝基(ONOO^-)含量。结果老年组缺血再灌注引起心肌细胞凋亡的程度明显高于成年组,凋亡指数分别为(14.6±1.7)%、(19.0±2.1)%,差异有统计学意义(P<0.05);caspase-3活性:成年组为(340±32)μmol/mg,老年组为(436±35)μmol/mg,差异有统计学意义(P<0.05);心肌组织中NOx含量:成年缺血再灌注组、老年缺血再灌注组分别为成年假手术组的(2.1±0.2)、(4.4±0.5)倍,差异有统计学意义(P<0.05);ONOO^-含量:成年缺血再灌注组和老年缺血再灌注组分别为(4.68±0.15)nmol/g、(7.25±0.18)nmol/g,差异有统计学意义(P<0.05)。结论老年大鼠对心肌缺血再灌注损伤的敏感性增加,可能的原因是老年鼠心脏中NO的毒性衍生物ONOO^-含量增加,从而导致功能蛋白的硝基化。 Objective To determine whether the susceptibility to ischemia-reperfusion injury in aged heart is higher than that in adult heart and, if so, to clarify the mechanisms underlying this change. Methods Wister rats (5- or 20-month-old) were randomly divided into 4 groups (6 animals in each group). The rats were subjected to 30 minutes of myocardial ischemia via ligating the left anterior descending coronary artery, followed by 3 hours of reperfusion (Young-MI/R group and Old-MI/R group) ; A silk suture around the left anterior descending coronary artery was not llgated in young and old rats (Young-sham group and Old-sham group). Myocardial apoptosis was detected by terminal deoxynucleotidyl transferase biotin-d UTP nick end labeling (TUNEL) staining and caspase-3 activity was detected by using a caspase-3 colorimetric assay. Nitrotyrosine content, a footprint of in vivo ONOOˉ formation, and total NO content were determined by ELISA and chemiluminescence method respectively. Results A significantly exacerbated cardiac reperfusion injury was found in OId-MI/R group as evidenced by increased TUNEL positive myocytes [(19.0±2. 1)% vs. (14.6± 1.7)%, and increased myocardial caspase-3 activity [ ( 436±35)/lmol/mg vs. ( 340 ± 32 )/μmol/mg] compared with Young-MI/R group(P〈0.05). Aged hearts had a markedly increased basal NOx level compared with young adult hearts. Marked higher myocardial nitrotyrosine content was found in OId-MI/R group[(7.25± 0. 18)mol/g] than that in Young-MI/R group [(4.68± 0. 15) nmol/g] (P〈0. 05) . Conclusions In aged hearts, high levels of NO might form highly toxic derivant, ONOOˉ , and its subsequent nitrified protein. This may attribute to the increased susceptibility of the aged heart to ischemic-reperfusion injury.
出处 《中华老年医学杂志》 CAS CSCD 北大核心 2006年第12期912-915,共4页 Chinese Journal of Geriatrics
关键词 心肌再灌注损伤 一氧化氮 过氧亚硝酸 Myocardial reperfusion injury Nitric oxide Peroxynitrous acid
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参考文献11

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同被引文献58

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