Division of Cardiovascular Surgery, Department of Surgery, and Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan, ROC.
Int J Cardiol. 2011 Jan 7;146(1):44-50. doi: 10.1016/j.ijcard.2009.06.012. Epub 2009 Jun 27.
BACKGROUND: The reported presence of DNA breaks, based on a positive reaction to the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end-labelling (TUNEL) assay, in fibrillating human right atria of cardiac valve disease may suggest apoptotic myocyte death. However, TUNEL positivity may reflect conditions other than cell death. METHODS: This study comprised 27 adult patients (14 patients with persistent atrial fibrillation and 13 in sinus rhythm) with significant mitral and tricuspid valve diseases. Atrial tissues were obtained during surgery. RESULTS: Immunohistochemical study demonstrated that 31.1±12.2% of the myocytes had TUNEL-positive nuclei in the fibrillating right atria whereas 37.4±23.2% of the myocytes had TUNEL-positive nuclei in the right atrial myocardium in sinus rhythm (p=0.505). However, most nuclei of TUNEL-positive myocytes in the right atria also expressed proliferating cell nuclear antigen (PCNA), an indicator of DNA replication and repair but never Ki-67, a replication-associated antigen (TUNEL(+)/PCNA(+) vs. TUNEL(+)/PCNA(-), 30.5±10.8% vs. 1.2±1.5%, p=0.005, in the atrial fibrillation group and 32.8±18.6% vs. 4.6±8.1%, p=0.003, in the sinus group), suggesting that most TUNEL-positive myocytes were undergoing DNA repair. In addition, the incidence of TUNEL-positive myocytes significantly and positively correlated with the incidence of PCNA-positive myocytes (r=0.5, p<0.03 in the right atria; r=0.661, p<0.04 in the left atria). CONCLUSIONS: Cell death by apoptosis occurs in a small percentage of atrial cardiomyocytes in mitral and tricuspid valve diseases and DNA repair is more important and preserves the cardiomyocytes.
背景：基于末端脱氧核苷酸转移酶（TdT）介导的 dUTP 原位缺口末端标记（TUNEL）检测到的 DNA 断裂的阳性反应，在心脏瓣膜病患者颤动的右心房中可能存在凋亡性心肌细胞死亡。然而，TUNEL 阳性可能反映了除细胞死亡以外的其他情况。
方法：本研究纳入了 27 名成人患者（14 名持续性心房颤动患者和 13 名窦性节律患者），他们均患有明显的二尖瓣和三尖瓣疾病。在手术期间获取心房组织。
结果：免疫组织化学研究表明，在颤动的右心房中，31.1%±12.2%的心肌细胞具有 TUNEL 阳性核，而在窦性节律的右心房心肌中，有 37.4%±23.2%的心肌细胞具有 TUNEL 阳性核（p=0.505）。然而，在右心房中，TUNEL 阳性心肌细胞的大多数核也表达了增殖细胞核抗原（PCNA），这是 DNA 复制和修复的指标，但从不表达 Ki-67，这是一种与复制相关的抗原（TUNEL(+)/PCNA(+) 比 TUNEL(+)/PCNA(-)，30.5%±10.8%比 1.2%±1.5%，在心房颤动组中，p=0.005；32.8%±18.6%比 4.6%±8.1%，p=0.003，在窦性节律组中），这表明大多数 TUNEL 阳性心肌细胞正在进行 DNA 修复。此外，TUNEL 阳性心肌细胞的发生率与 PCNA 阳性心肌细胞的发生率呈显著正相关（r=0.5，p<0.03，在右心房；r=0.661，p<0.04，在左心房）。
结论：在二尖瓣和三尖瓣疾病中，通过细胞凋亡发生的心肌细胞死亡占很小比例，而 DNA 修复更为重要，并且能保存心肌细胞。
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