益母草注射液小鼠急性毒性和Beagle犬重复给药毒性试验研究
Acute Toxicity of Leonurus japonicus Injection in Mice and Repeated Toxicity in Beagle Dogs

中文摘要：通过小鼠单次给药急性毒性试验和Beagle犬重复给药毒性试验，评价益母草注射液（YMC）的安全性。用半数致死剂量法对小鼠进行急性毒性试验，观察小鼠的死亡情况和急性毒性症状，用Bills法计算半致死剂量（LD 50）。将32只Beagle犬根据体质量、性别随机分为YMC 240.99 mg·kg -1、120.50 mg·kg -1、60.25 mg·kg -1组和0.9%氯化钠注射液对照组，每组8只。静脉滴注给药，每周给药6 d，连续180 d，停药恢复30 d。对Beagle犬进行临床症状、体质量、心电图、血液学、血液生化学、血清电解质、尿液及组织病理学等检查。YMC小鼠静脉给药LD 50为845.64 mg·kg -1，急性毒性症状主要表现为跳跃、烦躁、嗜睡、活动减少、阵挛性抽搐、眼球突出、尿失禁。重复给药毒性试验，Beagle犬出现呈剂量反应趋势的流涎、呕吐症状，未见肝、肾毒性，其余各项检测指标也均未见与药物毒性相关的明显异常。YMC小鼠静脉给药LD 50相当于临床拟用剂量的394.6倍，YMC重复给药毒性试验对Beagle犬的安全剂量为120.50 mg·kg -1，相当于临床拟用剂量的56.2倍。提示YMC具有较高的安全性。
英文摘要： Leonurus japonicus injection is used for regulating menstrual disturbances and invigorating blood circulation. This study aimed to evaluate the acute toxicity of L. japonicus injection in mice and repeated toxicity in Beagle dogs. The acute toxic symptoms and death induced by L. japonicus injection were observed in mice and the LD 50 was calculated by Bills method. In the repeated toxicity assay, 32 Beagle dogs were randomly divided into four groups (4 male and 4 female per group):control group (normal saline solution) and gradient L. japonicus injection treated groups (240.99 mg·kg -1, 120.50 mg·kg -1 and 60.25 mg·kg -1). Animals were intravenously administrated with L. japonicus injection by 6 days every week for 180 days followed by recovery for further 30 days.Subsequently, the weight, clinical signs, electrocardiogram, hematology, blood biochemical, serum electrolyte, urine and histopathology were examined. The LD 50 of L. japonicus injection was 845.64 mg·kg -1 in mice by intravenous administration, and the acute toxic symptoms were jumping, agitation, drowsiness, activity decrease, clinical convulsions, exophthalmos and incontinence. In the repeated toxicity study, Beagle dogs presented dose related hydrostomia and emesia rather than any other drug related adverse reaction. The LD 50 of L. japonicus injection was 845.64 mg·kg -1 in mice by intravenous administration, which equivalent to 394.6 times of clinical dose, and the safe dose in Beagle dogs was 120.50 mg·kg -1, which equivalent to 56.2 times of clinical dose, indicating that L. japonicus injection may have low toxicity. 2016,35(6): 871-878 收稿日期：2016-08-01 DOI：10.11984/j.issn.1000-7083.20160206 分类号：Q95-33 基金项目：四川省科技支撑计划项目（2014SZ0139） 作者简介：蒋文燕(1978-),女,助理研究员,主要从事药物非临床安全性评价研究,E-mail:38847251@qq.com *通讯作者：王红星,研究员,研究方向:药物非临床安全性评价研究,E-mail:whx6633@163.com 参考文献： 邓屾, 刘丽丽, 陈玥. 2014. 益母草化学成分研究Ⅲ[J]. 中国当代新医药论丛, 6:12-20. 冯群, 赵红, 孙蓉. 2014. 益母草临床应用和不良反应研究进展[J]. 中国药物警戒, 11(2):74-80. 何成军, 彭成, 戴鸥, 等. 2014. 益母草注射液化学成分研究[J]. 中草药, 45(21):3048-3052. 李晓宇, 冯群, 吕丽莉, 等. 2014.