后负荷增大引起的心肌肥厚过程中细胞凋亡的变化规律

Apoptosis in Pressure Overload-Induced Heart Hypertrophy

增大心脏后负荷引起心肌肥厚可诱导细胞凋亡 ,但心肌肥厚早期形成过程的凋亡情况及规律还未了解 ,本实验通过缩窄大鼠腹主动脉建立心肌肥厚模型来研究心肌肥厚早期形成过程的凋亡情况及规律。选取雄性SD大鼠 ,平均体重是 2 2 0 g,腹主动脉缩窄建立心肌肥厚模型并以缩窄时间的不同分组 ,采用脱氧核苷酸末端转移酶介导的缺口末端标记法 (TU NEL)的方法和流式细胞仪记数 (FCM)的方法检测细胞凋亡的比率。结果显示 :随着缩窄时间的延长 ,心脏肥厚指数和左心室肥厚指数均逐渐升高 ,在第 7d组达到最高值 ,维持此水平至 91d组 ,然后出现下降的趋势 ;用流式细胞仪记数 (FCM)的方法检测得到的细胞凋亡比率第 4d高于 0 d组 ,但差异不显著 ;由第 4d到第 7d,细胞凋亡比率显著下降 ;从 2 8d起 ,细胞凋亡比率出现回升的趋势 ,随着缩窄时间的延长 ,细胞凋亡比率逐渐升高 ,而 TUNEL 的结果与此结果基本一致。结论 :细胞凋亡参与了心肌肥厚早期的形成过程。心肌由健康状态向肥厚转变的过程中 ,在腹主动脉缩窄时间较短的时段内凋亡和肥厚这两个因素相互作用维持生长消亡的平衡 ,来调节心脏的功能 ,于腹主动脉缩窄时间较长的时段内 ,在病理因子的刺激下凋亡数目继续增多 。

Pressure overload can result in heart hypertrophy, and induce apoptosis, but the phenomenon of apoptosis during the forepart of cardiomyocyte hypertrophy remains unclear. The aim of this study was to inquire into the process of cardiomyocyte apoptosis during the forepart of cardiomyocyte hypertrophy. We constructed the hypertrophy model by transverse aortic constriction of male SD rat. The apoptosis ratio was detected by TUNEL method and FCM. The result demonstrated that hypertrophy indexes increased with the time of constriction, reached the highest level at day 7, maintained that level, and then decreased at day 91. The apoptosis ratio of cardiomyocyte at day 4 was higher than that at day 0 detected by FCM method, and the ratio at day 7 was markedly lower than that at day 4. After day 28, the apoptosis ratio of cardiomyocyte went up again with the time of constriction after surgery. TUNEL method revealed that positive nuclei were observed in cardiomyocytes exclusively in the left ventricle; the apoptosis ratio increased when constriction continued. TUNEL method confirmed the result of FCM. These data indicate that cardiac hypertrophy is initiated by apoptosis of cardiomyocyte, these two factors(hypertrophy and apoptosis) maintain the balance between growth and death during the early short period of aortic constriction, and when aortic constriction goes on they are involved in the pathogenesis of heart remodeling.