实验性心衰大鼠中的心肌细胞凋亡及去甲肾上腺素含量的变化

Changes of Cardiomyocyte Apoptosis and Norepinephrine Concentration in Heart Failure Wistar Rats

目的 心肌在由代偿性肥厚到心衰的转变过程中 ,伴有明显的心肌细胞数目下降以及收缩力减低。我们假设心肌细胞数目的减少以及功能的丧失可能与心肌细胞凋亡数目增加有关 ,而血中去甲肾上腺素含量增高可能促进这一过程。方法 为了检验这个假说 ,我们在实验性高血压大鼠 (EHR)模型的基础上 ,采用原位末端脱氧核糖核苷酸转移酶介导的dUTP缺口末端标记法 (terminaldeoxynucleotiyltransferase mediateddUTPnickendlabeling ,TUNEL)观察了发生心衰的实验性高血压大鼠 (EHR F组 )和同期未发生心衰的实验性高血压大鼠 (EHR NF组 )的心肌细胞凋亡状况 ,同时用改良荧光法测定了EHR F组、EHR NF组以及对照组外周血及心腔内血中的去甲肾上腺素含量 ,以探讨血中儿茶酚胺含量与心肌细胞凋亡的关系以及二者在心衰发展过程中的作用。结果 对照组心肌中未发现有心肌细胞凋亡 ,而EHR F组和EHR NF组均有心肌细胞凋亡发生 ,但心衰组心肌细胞凋亡的数目明显高于对照组。大鼠经腹主动脉结扎 2周后 ,未发生心衰的EHR NF组大鼠外周及心内血的去甲肾上腺素水平均显著性高于对照组 (P <0 .0 5 ) ,其外周和心内去甲肾上腺素含量之间无显著性差异 ;而出现心衰的大鼠其外周和心内去甲肾上腺素水平明显高于EHR NF组 ,差异有极显著?

Aim The transition from compensated ventricular hypertrophy to failure is associated with a marked reduction in myocyte mass and reduction in maximum Ca 2+ activated myofibrillar force. We hypothesized that the reduction in myocyte mass and the functional loss may be ascribed to the increased cell death by apoptosis, while the increased plasma norepinephrine may accelerate the process. Method\ apoptosis were determined by the method of terminal deoxynucleotidyltransferase mediated dUTP nick end labeling in the experimental hypertensive rat models (EHR) and in normal heart (control group)from Wistar rat, the content of norepinephrine in peripheral and cardiac blood from three groups was mensuraed by the modified fluorescence method. Results The data showed that no apoptotic cells were found in control group, while apoptotic cells were found in both heart failing group (EHR\|F) and non\|heart failing group (EHR-NF). The number of apoptotic cells in EHR F group increased significantly compared with that in EHR NF group. The level of norepinephrine in the hypertension rat increased significantly compares with that in control group. There was no significant difference in NE concentration between the cardiac blood and peripheral blood in EHR NF group, though the NE concentration of cardiac and peripheral blood in EHR NF group was increased significantly( P <0.05)than that in control group. When the heart failure occurred, NE concentration of cardiac and peripheral blood increased very significantly( P <0.01) than that in non failing group. Moreover, the NE concentration in cardiac blood was significantly higher than that in peripheral blood( P <0.05). Conclusion Increased cardiomyocyte apoptosis may be the important mechanism during the transition from compensated hypertrophy to heart failure in experimental hypertensive rat. High level of norepinephrine in blood, especially in cardiac blood, may be associated with the process.