Age-related difference in myocardial function and inflammation in a rat model of myocardial ischemia-reperfusion
Age-related difference in myocardial function and inflammation in a rat model of myocardial ischemia-reperfusion
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DOI：
10.1016/s0008-6363(02)00603-x
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发表时间：
2002-12-01
影响因子：
10.8
通讯作者：
Hock, CE
中科院分区：
文献类型：
--
作者：
Liu, PT;Xu, BH;Hock, CE
目的：与年轻人相比，衰老与心肌缺血再灌注损伤耐受性降低有关。然而，在体内心肌缺血再灌注（MI/R）过程中，关于心肌功能和炎症的年龄相关变化的文献很少。方法：在大鼠心肌缺血再灌注（MI/R）模型中，我们检测心肌细胞凋亡和炎症反应的年龄相关差异。老龄（19月龄）和幼龄（4月龄）雄性F344 BN大鼠结扎左冠状动脉主干心肌缺血30 min，然后解除结扎，再灌注4 h。实验分为青年假对照组、老年假对照组、青年心肌梗死/再灌注大鼠和老年心肌梗死/再灌注大鼠4组。结果：与老龄大鼠相比，MI/R诱导年轻大鼠心脏缺血区域循环白细胞增加78%，超氧化物生成增加30%。心肌梗死/心肌梗死后，幼龄大鼠心律失常评分高于老龄大鼠（P=0.058）。年轻假药大鼠和老年假药大鼠的血流动力学无差异。然而，与MI/R后的年轻大鼠相比，老龄大鼠的心脏指数在再灌注3小时时下降了34%，在再灌注4小时时下降了33%。此外，在2、3时，脑卒中容积指数分别下降了54%、56%和65%。老龄大鼠的再灌注时间和再灌注时间分别为4 h。ELISA和TUNEL染色显示，老年大鼠心肌细胞凋亡较年轻大鼠明显增加。有趣的是，RT-PCR分析显示，与年轻大鼠相比，MI/R显著增加了老年大鼠Bax mRNA与Bcl-2 mRNA的比值（3.51比0.74）。结论：与老年大鼠相比，MI/R与年轻大鼠心脏缺血周围循环白细胞的增加和超氧化物的产生有关。然而，与年轻大鼠相比，心肌梗死/再灌注可显著降低老年大鼠的心脏指数和脑卒中容量指数。此外，老年大鼠在MI/R后表现出Bax mRNA与Bcl-2 mRNA的比例增加和心肌细胞凋亡，这可能至少部分解释了心肌功能障碍加剧的原因。(C) 2002 Elsevier Science B.V.版权所有
Objective: Aging is associated with a reduced tolerance to myocardial ischemia reperfusion injury when compared to the young adult. However, there is very little information in the literature regarding age-related changes in myocardial function and inflammation during myocardial ischemia-reperfusion (MI/R) in vivo. Methods: We examined age-related differences in myocyte apoptosis and the inflammatory response in a rat model of myocardial ischemia-reperfusion (MI/R). The aged (19 months) and young (4 months) male F344 BN rats were subjected to 30 min of myocardial ischemia by ligating the left main coronary artery, followed by release of the ligature and 4 h of reperfusion. Four experimental groups, e.g. young sham control, aged sham control, young rats subjected to MI/R, and aged rats subjected to MI/R, were studied. Results: MI/R induced a 78% increase in circulating leukocytes and a 30% increase in superoxide generation in the ischemic region of the heart of young rats, when compared to aged rats. Moreover, the arrhythmia scores were higher in young rats than in aged rats (P=0.058) following MI/R. There was no difference in hemodynamics between young sham and aged sham rats. However, the cardiac index was decreased by 34% at 3 h of reperfusion and by 33% at 4 h of reperfusion in aged rats, when compared to young rats following MI/R. Furthermore, stroke volume index was decreased by 54, 56, and 65% at 2, 3. and 4 h of reperfusion in aged rats, respectively, when compared that of young rats subjected to MI/R. There was an enhanced myocyte apoptosis, as indicated by ELISA and TUNEL staining in the myocardium of aged rats compared to young rats following MI/R. Interestingly, RT-PCR analysis indicated that MI/R significantly increased the ratio of Bax mRNA to Bcl-2 mRNA in aged rats compared to that of young rats (3.51 vs. 0.74). Conclusion: MI/R is associated with an increase in circulating leukocytes and generation of superoxide in the peri-ischemic areas of the heart of young rats, compared to aged rats. However, MI/R induces a significant decrease in cardiac index and stroke volume index in aged rats, when compared to young rats following MI/R. Furthermore, aged rats exhibit an increase ill the ratio of Bax mRNA to Bcl-2 mRNA and cardiomyocyte apoptosis following MI/R, which may explain, at least in part, the enhanced myocardial dysfunction. (C) 2002 Elsevier Science B.V. All rights reserved.