Oh J, So H S, Park R, Ryu D K, Moon B S, Park O K, Chung Y T
Department of Anatomy, Wonkwang University School of Medicine, Iksan, Chonbuk, South Korea.
Immunopharmacol Immunotoxicol. 2000 May;22(2):297-315. doi: 10.3109/08923970009016422.
Jagamchotang has been used for treatment of ischemic myocardial diseases in Chinese traditional medicine. However, little is known about the mechanism by which Jagamchotang rescues myocardial cells from ischemic damages. To elucidate the protective mechanisms, the effects of Jagamchotang on ischemia/reperfusion-induced cytotoxicity and generation of nitric oxide (NO) are investigated in primary neonatal myocardial cells. Ischemia/reperfusion itself induces severe myocardial cell death in vitro. However, treatment of the cells with Jagamchotang significantly reduces both ischemia/reperfusion-induced myocardial cell death and LDH release. In addition, pretreatment of Jagamchotang before reperfusion recovers the lose of beating rates after ischemia/reperfusion. For a while, the water extract of Jagamchotang stimulates myocardial cells in ischemic condition to produce nitric oxide (NO) in a dose dependent manner and it protects the damage of myocardial cells. Furthermore, the protective effects of the water extract of Jagamchotang is mimicked by treatment of sodium nitroprusside, an exogenous NO donor. NG-monomethyi-L-argine (NGMMA), a specific inhibitor of nitric oxide synthase (NOS), significantly blocks the protective effects of Jagamchotang on the cells after ischemia/reperfusion. Taken together, we suggest that the protective effects of Jagamchotang against ischemia/reperfusion-induced myocardial damages may be mediated by NO production during ischemic condition.
加味逍遥汤在传统中医中一直被用于治疗缺血性心肌病。然而,关于加味逍遥汤挽救心肌细胞免受缺血损伤的机制却知之甚少。为了阐明其保护机制,我们在原代新生心肌细胞中研究了加味逍遥汤对缺血/再灌注诱导的细胞毒性和一氧化氮(NO)生成的影响。缺血/再灌注本身在体外会诱导严重的心肌细胞死亡。然而,用加味逍遥汤处理细胞可显著减少缺血/再灌注诱导的心肌细胞死亡和乳酸脱氢酶(LDH)释放。此外,在再灌注前用加味逍遥汤预处理可恢复缺血/再灌注后心率的降低。同时,加味逍遥汤的水提取物能以剂量依赖的方式刺激缺血状态下的心肌细胞产生一氧化氮(NO),并保护心肌细胞免受损伤。此外,外源性NO供体硝普钠的处理可模拟加味逍遥汤水提取物的保护作用。一氧化氮合酶(NOS)的特异性抑制剂NG-单甲基-L-精氨酸(NGMMA)可显著阻断加味逍遥汤对缺血/再灌注后细胞的保护作用。综上所述,我们认为加味逍遥汤对缺血/再灌注诱导的心肌损伤的保护作用可能是通过缺血状态下NO的产生介导的。