Zhao Qun, Yang Min, Deng Yanping, Yu Haitao, Wang Linlin, Teng Fukang, Cho Kenka, Ma Hongmei, Wu Peng, Li Xue, Wu Wanying, Liu Xuan, Xu Feng, Jiang Baohong, Guo De-An
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road #501, Shanghai 201203, China.
Shenyang Pharmaceutical University, Wenhua Road #103, Shenyang 110016, China.
Int J Mol Sci. 2015 Dec 9;16(12):29345-56. doi: 10.3390/ijms161226176.
Our previous study indicated that the combination of salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1), the main components of Salvia miltiorrhizae and Panax notoginseng, improves myocardium structure and ventricular function in rats with ischemia/reperfusion injury. The present study aimed to determine the safety of the combined SalB and Rg1 (SalB-Rg1) in mice. The safety of SalB-Rg1 was evaluated through acute toxicity and repeated-dose toxicity. In the acute toxicity study, the up and down procedure was carried out firstly, and then, the Bliss method was applied. In the toxicity study for seven-day repeated treatment of SalB-Rg1, forty Kunming mice were randomly divided into four groups. The intravenous median lethal dose (LD50) of the SalB-Rg1 combination was 1747 mg/kg using the Bliss method. For both the acute toxicity study and the seven-day repeated toxicity study, SalB-Rg1 did not induce significant abnormality on brain, heart, kidney, liver and lung structure at any dose based on H&E stain. There were no significant changes related to the SalB-Rg1 toxicity detected on biochemical parameters for two kinds of toxicity studies. The LD50 in mice was 1747 mg/kg, which was more than one hundred times higher than the effective dose. Both studies of acute toxicity and seven-day repeated dose toxicity indicated the safety of the SalB-Rg1 combination.
我们之前的研究表明，丹参和三七的主要成分丹酚酸B（SalB）与人参皂苷Rg1（Rg1）联合使用，可改善缺血/再灌注损伤大鼠的心肌结构和心室功能。本研究旨在确定联合使用SalB和Rg1（SalB-Rg1）对小鼠的安全性。通过急性毒性和重复给药毒性评估SalB-Rg1的安全性。在急性毒性研究中，首先采用序贯法，然后应用Bliss法。在SalB-Rg1连续7天重复给药的毒性研究中，将40只昆明小鼠随机分为四组。采用Bliss法测得SalB-Rg1组合的静脉注射半数致死量（LD50）为1747 mg/kg。在急性毒性研究和7天重复毒性研究中，基于苏木精-伊红（H&E）染色，SalB-Rg1在任何剂量下均未引起脑、心、肾、肝和肺结构的显著异常。在两种毒性研究的生化参数方面，未检测到与SalB-Rg1毒性相关的显著变化。小鼠的LD50为1747 mg/kg，比有效剂量高出一百多倍。急性毒性和7天重复剂量毒性研究均表明SalB-Rg1组合具有安全性。
