Li Lang, Su Qiang, Wang Yan, Su Bo, Dai Ri-xin, Lu Yong-guang, Wu Xiang-hong, Liu Tang-wei
Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2010 Apr;38(4):363-8.
To investigate the dynamic changes of cardiomyocyte apoptosis and the role of death receptor apoptotic pathway in a rat model of coronary microembolization (CME).
Adult rats were randomized to coronary microembolization (CME group, n = 63) or sham-operated group (S group, n = 55). CME model was established by aortic injection of 0.1 ml microspheres (42 microm, 3 x 10(4)/ml) into the left ventricle when the ascending aorta was temporarily clamped.S group received 0.1 ml saline injection and survived rats were randomly examined at 0, 3, 6, 12 and 24 hour post CME (n = 10 each). Heart function was evaluated by echocardiography. Myocardium sample was stained with hematoxylin-eosin and hematoxylin-basic fuchsin-picric acid to detect infarct areas. Cardiomyocyte apoptosis was detected with TUNEL staining. The expression of caspase-3 and caspase-8 was measured by Western blot analysis.
Compared with S group, the left ventricular ejection fraction was significantly decreased and left ventricular end-diastolic diameter was significantly increased in CME group (all P < 0.05) except 0 hour CME group. The infarct sizes were similar in 3 hour, 6 hour, 12 hour, and 24 hour CME groups (P > 0.05). The apoptosis index (AI) in CME group were significantly higher at each time point compared to S group (P < 0.05) except 0 hour CME group and peaked at 6 hours. Apoptotic cardiomyocytes were found mainly in the myocardial microinfarcted area and border zones. The relative expression of caspase-3 and caspase-8 in CME group were both significantly increased at 3 hours and peaked at 6 hour post CME (P < 0.05).
Cardiomyocytes apoptosis was significantly increased after coronary microembolization via activating death receptor apoptotic pathway in this coronary microembolization model.
探讨冠状动脉微栓塞（CME）大鼠模型中心肌细胞凋亡的动态变化及死亡受体凋亡途径的作用。
将成年大鼠随机分为冠状动脉微栓塞组（CME组，n = 63）和假手术组（S组，n = 55）。在升主动脉暂时夹闭时，经主动脉向左心室注射0.1 ml微球（42微米，3×10⁴/ml）建立CME模型。S组注射0.1 ml生理盐水，对存活大鼠在CME后0、3、6、12和24小时进行随机检查（每组n = 10）。通过超声心动图评估心功能。心肌样本用苏木精-伊红和苏木精-碱性品红-苦味酸染色以检测梗死面积。用TUNEL染色检测心肌细胞凋亡。通过蛋白质免疫印迹分析测定caspase-3和caspase-8的表达。
与S组相比，除CME后0小时组外，CME组左心室射血分数显著降低，左心室舒张末期直径显著增加（均P < 0.05）。CME后3小时、6小时、12小时和24小时组的梗死面积相似（P > 0.05）。除CME后0小时组外，CME组各时间点的凋亡指数（AI）均显著高于S组（P < 0.05），并在6小时达到峰值。凋亡心肌细胞主要见于心肌微梗死区和边缘区。CME组caspase-3和caspase-8的相对表达在CME后3小时均显著增加，并在CME后6小时达到峰值（P < 0.05）。
在该冠状动脉微栓塞模型中，冠状动脉微栓塞后通过激活死亡受体凋亡途径，心肌细胞凋亡显著增加。
