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丹参酚酸B与人参皂苷Rg1联合应用对小鼠的安全性评价

The Safety Evaluation of Salvianolic Acid B and Ginsenoside Rg1 Combination on Mice.

作者信息

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

机构信息

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road #501, Shanghai 201203, China.

Shenyang Pharmaceutical University, Wenhua Road #103, Shenyang 110016, China.

出版信息

Int J Mol Sci. 2015 Dec 9;16(12):29345-56. doi: 10.3390/ijms161226176.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54fb/4691119/6e2ebcd66d74/ijms-16-26176-g001.jpg

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