关键词：高血压；心肌；细胞
【摘要】 目的 探讨心肌细胞凋亡在自发性高血压大鼠(SHR)心脏重塑中的作用及其意义。方法 采用末端脱氧核糖核苷酸转移酶介导的带荧光的dUTP缺口末端标记法(TUNEL)和透射电子显微镜技术,观察不同年龄SHR心肌细胞凋亡的变化及其规律。结果 (1)1月龄SHR组[无左室肥厚组(NLVH组)]和18～20月龄SHR组[充血性心力衰竭组(CHF组)]凋亡的心肌细胞核数目和凋亡指数显著增加(P均<0.01)，10月龄SHR组[左室肥厚组(LVH组)]则显著减少(P均<0.01)。(2)有LVH的SHR中,心肌细胞凋亡与LVH呈显著负相关(P<0.01)。(3)透射电子显微镜检查发现NLVH组和CHF组SHR左心室心肌组织中可见具有凋亡形态学特征的凋亡心肌细胞(胞质浓缩、胞核染色质浓聚边集)，LVH组和CHF组可见心肌细胞肥大、肌浆网扩张和线粒体增生等改变。结论 (1)SHRLVH发生前和出现CHF后其心肌细胞凋亡显著增加；SHR伴显著LVH时其心肌细胞凋亡显著减少。提示心肌细胞凋亡在SHR心脏重塑中起重要作用，心肌细胞凋亡减少可能与LVH有关，而心肌细胞凋亡增多可能与CHF有关。(2)在SHR高血压→LVH→心力衰竭演进过程中存在心肌细胞凋亡的动态变化，可根据这一过程中心肌细胞凋亡的时间窗选用刺激或抑制心肌细胞凋亡的策略来改善高血压心脏重塑。
Changes and significance ofcardiac myocyte apoptosis in spontaneously hypertensive rat
LI Faqi, CHEN Yunzhen. Department of Cardiology, First AffiliatedHospital, Chongqing Medical University, Chongqing 400016
【 Abstract 】 Objective To study the effects and significance of cardiomyocyteapoptosis participating in the cardiac remodeling of spontaneously hypertensive rats(SHR). Methods Weinvestigated the dynamic changes of cardiac myocyte apoptosis in left ventricle of SHR andWistar-Kyoto rats (WKY) using in situ TdT-mediated dUTP nick end labeling (TUNEL) andtransmission electron microscope.Results (1)Apoptotic myocyte nuclei and apoptotic index (calculated bydividing the number of apoptotic myocyte nuclei by the total number of myocyte nuclei andmultiplying that value by 100) were higher in 1-month-old SHR group [ no left ventricular hypertrophy (NLVH) group ] and 18-20-month-old SHR group [ congestive heart failure (CHF)group ] than those inage -matched WKY group respectively (all P values less than 0.01). Apoptotic myocytenuclei and apoptotic index were lower in 10-month-old SHR [ left ventricular hypertrophy (LVH) group ] than those in age-matched WKYgroup, NLVH group and CHF group (all P values less than 0.01). (2) Apoptotic index wasinversely correlated with left ventricular hypertrophic index in SHR with LVH and CHF(n=6, r=-0.90, P<0.01, y=3.24-0.09x; n=5, r=-0.87, P<0.01, y=4.76-0.02x). (3)Electron microscopic features of cardiocyte apoptosis (including intact sarcolemma in thepresence of cytoplasm compaction and segregation of nuclear chromatin into small sharplydelineated electron dense masses that abut the nuclear envelope) were identified in leftventricular tissue obtained from SHR with NLVH group and CHF group but in none of thetissue specimens obtained from the left ventricles of the others. The ultramicrostructuralchanges, such as cardiac cellular hypertrophy, sarcoplasmic reticulum expansion,mitochondrion hyperplasia, occurred in left ventricular tissue obtained from SHR with LVHgroup and CHF group.Conclusion (1) Cardiac myocyte apoptosis increases significantly in the leftventricle of SHR with CHF and without LVH. However, cardiomyocyte apoptosis decreasesmarkedly in the left ventricle of SHR with LVH. These findings suggest that cardiacmyocyte apoptosis may play a key role in the heart remodeling of SHR, and thatcardiomyocyte apoptosis decreasing may be bound up with LVH and cardiac myocyte apoptosisincreasing may be related with CHF of SHR. (2) The dynamic changes of cardiac cellapoptosis occur in the hypertension → LVH → heart failure volving process. It is possible that the heartremodeling is ameliorated by the therapeutic strategies of stimulating or suppressingcardiomycoyte apoptosis according to the time window of cardiac cell apoptosis in theabove process.
【 Key words 】 hypertension myocardium cells
细胞凋亡,又称程序性细胞死亡 ......
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