自发性高血压大鼠左心室重构中的细胞凋亡

Apoptosis in Left Ventricular Remodeling of Spontaneously Hypertensive Rats

为探讨细胞凋亡在高血压大鼠左心室重构中的变化及其作用 ,以 16周龄雄性自发性高血压大鼠和正常血压对照大鼠为研究对象 ,左心室中轴切片 ,应用TdT介导的dUTP缺口末端标记法检测心肌组织细胞凋亡 ,透射电镜观察凋亡细胞的超微结构和细胞类型 ,LSAB免疫组织化学法检测细胞膜死亡受体分子Fas蛋白的细胞定位。结果发现 ,与同龄正常血压对照大鼠相比较 ,16周龄自发性高血压大鼠左心室肥厚指数显著增高 ;光镜观察发现 ,心肌细胞凋亡指数显著增加 [以 10 4 个核为计算单位 (下同 ) ,自发性高血压组为 19.5 4± 7.2 7,正常血压对照组为 6 .92± 4.35 ,P <0 .0 5 ],并可见小血管内皮细胞和浸润心肌的白细胞凋亡 ,但纤维细胞凋亡指数显著下降 (自发性高血压组为 5 .88± 2 .15 ,正常血压对照组为 14.34± 9.5 6 ,P <0 .0 5 )。电镜观察发现 ,自发性高血压大鼠可见凋亡的内皮细胞和心肌细胞 ,内皮细胞凋亡多发生于萎缩的毛细血管 ,血管周围有纤维组织增生 ;正常血压对照大鼠可见凋亡的纤维细胞。Fas蛋白在自发性高血压大鼠主要定位于心肌细胞 ,在正常血压对照大鼠主要定位于纤维细胞。实验提示高血压左心室重构中细胞凋亡类型发生了改变 ,Fas受体途径可能与此改变有关。

Aim In order to study the change and role of apoptosis in hypertensive left ventricular remodeling. Methods Hearts from 16-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY) were investigated. Apoptosis in left ventricle sections was assessed by an in situ end-labeling technique (TUNEL), the feature and type of cells undergoing apoptosis were identified ultrastructurally by transmission electron microscope (ECM). Additionally, localization of Fas protein- a mediator of apoptotic cell death was examined by immunohistochemistry. Results Compared with 16-week-old WKY, 16-week-old SHR exhibited increased hypertrophic index, the apoptotic frequency of myocytes was also increased(19.54±7.27 vs 6.92±4.35/104 nucleus,P<0.05), whereas the apoptotic frequency of fibroblasts was significantly decreased (5.88±2.15 vs 14.34±9.56/104 nucleus, P<0.05). Moreover, apoptotic endothelial cells and leukocytes infiltrated into myocardium were also identified in SHR. Features of apoptotic myocytes and endothelial cells were observed by ECM in SHR. The latter often occurred in shrunken capillaries surrounded by collagen fragments The distribution of Fas antigen protein was mainly confined to myocytes in SHR, but limited to interstitial fibroblasts in WKY, consistently with the type of cells undergoing apoptosis in these two strains. Conclusion This study first suggest that apoptosis of different cell type may work synthetically in hypertensive myocardial remodeling, and Fas antigen may be associated with the mechanisms of these apoptotic process. Our findings also have important significance in searching new avenues for treatment with appropriate site-specific physiological or pharmacological regulators of apoptosis.