Department of Cardio-Angiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Japan.
Circ J. 2011;75(3):662-71. doi: 10.1253/circj.cj-10-0673. Epub 2010 Dec 24.
Electrical and structural remodeling, characterized by prolonged action potential duration (APD), Kv4.2 downregulation and cellular infiltration were studied in rat experimental autoimmune myocarditis (EAM). Because the reactive oxygen species (ROS) has been speculated to play a role in the promotion of such remodeling, the effect of N-acetylcysteine (NAC) on the progression of ventricular remodeling was evaluated.
Six-week-old Lewis rats were immunized with porcine cardiac myosin. On Days 10-11 after the immunization, NAC (0, 1, 10, or 100mg) was injected intraperitoneally to EAM and control rats. On Day 14, the electrophysiological parameters were evaluated and the expression levels of the mRNA were examined by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR).The EAM rats exhibited a typical acute myocarditis with prolonged APD and reduced Kv4.2 expression as previously reported. The myocarditis and electrical changes were significantly suppressed by NAC-treatment in a dose-dependent manner (P<0.05). In rats with 100mg NAC, the myocarditis was almost totally negated although the mortality increased. In rats with 1mg NAC, the suppression of myocarditis was not obvious, but APD prolongation and Kv4.2 reduction was attenuated (P<0.05).
The NAC treatment suppressed ventricular remodeling in the EAM rats. This may indicate the role of oxidative stress in causing remodeling and myocarditis itself in the acute phase of myocarditis.
在大鼠实验性自身免疫性心肌炎（EAM）中，研究了电重构和结构重构，其特征为动作电位持续时间（APD）延长、Kv4.2 下调和细胞浸润。因为活性氧（ROS）被推测在促进这种重构中发挥作用，所以评估了 N-乙酰半胱氨酸（NAC）对心室重构进展的影响。
6 周龄的Lewis 大鼠用猪心肌球蛋白免疫。在免疫后第 10-11 天，将 NAC（0、1、10 或 100mg）腹膜内注射到 EAM 和对照大鼠中。在第 14 天，评估电生理参数，并通过实时定量逆转录聚合酶链反应（RT-PCR）检查 mRNA 的表达水平。如先前报道的那样，EAM 大鼠表现出典型的急性心肌炎，伴有 APD 延长和 Kv4.2 表达减少。NAC 处理以剂量依赖性方式显著抑制心肌炎和电变化（P<0.05）。在接受 100mg NAC 治疗的大鼠中，尽管死亡率增加，但心肌炎几乎完全被抑制。在接受 1mg NAC 治疗的大鼠中，心肌炎的抑制不明显，但 APD 延长和 Kv4.2 减少得到减轻（P<0.05）。
NAC 治疗抑制了 EAM 大鼠的心室重构。这可能表明氧化应激在引起重构以及心肌炎本身在心肌炎急性期中的作用。
