Shimada Kana, Uzui Hiroyasu, Ueda Takanori, Lee Jong-Dae, Kishimoto Chiharu
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
First Department of Internal Medicine, Faculty of Medical Science, University of Fukui, Fukui, Japan.
J Cardiovasc Pharmacol Ther. 2015 Mar;20(2):203-10. doi: 10.1177/1074248414547574. Epub 2014 Aug 20.
Oxidative stress may play an important role in the development of myocarditis. We investigated the effects of N-acetylcysteine (NAC), a potent antioxidant, on experimental autoimmune myocarditis (EAM) in rats.
A rat model of porcine myosin-induced EAM was used. After the immunization with myosin, NAC (20 mg/kg/d) or saline was injected intraperitoneally on days 1 to 21. Additional myosin-immunized rats treated with NAC were orally given 25 mg/kg/d of N(G)-nitro-l-arginine methylester (l-NAME), an inhibitor of nitric oxide (NO) synthase, and N(G)-nitro-d-arginine methylester (d-NAME), an inactive enantiomer. The NAC treatment improved cardiac pathology associated with reduced superoxide production. In the EAM rats treated with NAC associated with oral l-NAME, but not with oral d-NAME, the severity of myocarditis was not reduced. Expression of intercellular adhesion molecule 1 was reduced by NAC treatment. Myocardial c-kit(+) cells were demonstrated only in the NAC-treated group. Hemodynamic study showed that the increased left ventricular mass produced by myocardial inflammation tended to be reduced by NAC treatment.
Treatment with NAC ameliorated myocardial injury via NO system in a rat model of myocarditis.
氧化应激可能在心肌炎的发展中起重要作用。我们研究了强效抗氧化剂N-乙酰半胱氨酸（NAC）对大鼠实验性自身免疫性心肌炎（EAM）的影响。
采用猪肌球蛋白诱导的EAM大鼠模型。用肌球蛋白免疫后，在第1至21天腹腔注射NAC（20 mg/kg/d）或生理盐水。另外，用NAC治疗的经肌球蛋白免疫的大鼠口服给予25 mg/kg/d的一氧化氮（NO）合酶抑制剂N（G）-硝基-L-精氨酸甲酯（L-NAME）和无活性对映体N（G）-硝基-D-精氨酸甲酯（D-NAME）。NAC治疗改善了与超氧化物产生减少相关的心脏病理。在口服L-NAME而非口服D-NAME的NAC治疗的EAM大鼠中，心肌炎的严重程度未降低。NAC治疗降低了细胞间黏附分子1的表达。仅在NAC治疗组中发现心肌c-kit（+）细胞。血流动力学研究表明，NAC治疗倾向于减轻心肌炎症引起的左心室质量增加。
在心肌炎大鼠模型中，NAC治疗通过NO系统改善了心肌损伤。
