高血压大鼠心脏肥厚过程中心肌细胞凋亡心肌纤维化动态观察

Dynamic Changes of Cardiomyocyte Apoptosis and Myocardial Fibrosis During the Development of Cardiac Hypertrophy in Hypertensive Rats

目的 探讨SHR心脏肥厚进展阶段心肌细胞凋亡、心肌纤维化及左室重构特点及其相互关系。方法 分别采用末端脱氧核糖核苷酸转移酶介导dUTP缺口末端标记 (TUNEL)、放射免疫测定及病理检查方法对 16周龄、2 4周龄、32周龄SHR心肌细胞凋亡指数 (APOI)、心肌胶原容积分数 (CVF)和心肌血管周围胶原面积 (PVCA)、血浆和组织血管紧张素Ⅱ检测 ,并以同龄Wister大鼠作对照。结果 与同龄正常血压Wistar大鼠比较 ,SHR各周龄组收缩压明显增高、心脏肥厚指标心脏重量 (HW)、左室重量 (LVW )、左室重量指数 (LVW /BW )均显著增加 ;各周龄组SHR心肌细胞APOI显著增加 ,各周龄组间无显著性差异 ;各周龄组SHR大鼠血浆、心肌组织AngⅡ明显增高 ;2 4、32周龄SHR的CVF和PVCA显著增加 ;SHR心肌组织AngⅡ分别与APOI、CVF呈显著正相关 ,APOI与CVF呈显著正相关。结论 心肌细胞凋亡与心肌纤维化参与SHR代偿性心脏肥厚阶段心脏重构病理过程 ,组织AngⅡ是导致SHR代偿性心脏肥厚阶段心肌细胞凋亡与心肌纤维化的重要机制之一。

Objective To investigate dynamic changes of cardiomyocyte apoptosis and myocardial fibrosis during the development of cardiac hypertrophy in the spontaneously hypertensive rats(SHR). Methods We studied the hearts specimens from 16,24 and 32 weeks old SHRs and age matched Wister Kyoto rats(WKY). Cardiomyocyte apoptosis was identified by in situ TDT mediated dUTP nick end labeling(TUNEL). The collagen volume fraction (CVF) and perivascular circumferential area (PVCA) were measured by pathological examination. The plasma and myocardium angiotensinⅡ were determined by radioimmunoassay. Results The results showed that(1)The systolic blood pressure,heart and left ventricular weights and left ventricular mass index were higher significantly in the SHRs of three age groups than in the WKY rats of age matched groups. (2) Compared with the WKY rats of age matched groups,the apoptotic index,CVF and PVCA were increased significantly, but no significant differences found among three groups in SHRs. (3)Plasma and myocardium angiotensinⅡ were increased significantly in the SHRs,and were positively correlated with cardiomyocyte apoptotic index and CVF respectively. Conclusion Myocardium angiotensinⅡ is one of potential mechamisms in induction of cardiomyocyte apoptosis and myocardial fibrosis.