脯氨酸丹参素冰片酯对小鼠急性毒性研究  

Acute toxicity of proline Danshensu borneol ester in mice

作　　者：王荣 刘自群 王娜娜 谭雄 张怡心 杨宽 秦蓓 WANG Rong;LIU Ziqun;WANG Nana;TAN Xiong;ZHANG Yixin;YANG Kuan;QIN Bei(Institute of Drug Research,Xi’an Medical College,Xi’an Key Laboratory of Multi Synergistic Antihypertensive Innovative Drug Development,Xi’an Shaanxi 710021,China;College of Pharmacy,Chengdu Medical College,Chengdu Sichuan 610500,China)

机构地区：[1]西安医学院药学院药物研究所,西安市多靶协同抗高血压创新药物研制重点实验室,陕西西安710021 [2]成都医学院药学院,四川成都610500

出　　处：《中国药物警戒》2023年第7期754-757,共4页Chinese Journal of Pharmacovigilance

基　　金：国家自然科学基金资助项目(81903288);陕西省重点研发计划项目(2021ZDLSF03-05);西安医学院校级科技创新团队(2021TD03、2021TD07);西安医学院校级重点药学学科(西医发[2019]96号);西安医学院校级大学生创新创业训练计划项目(121522107);陕西省大学生创新创业训练计划项目(S202111840030)。

摘　　要：目的探究抗高血压1类新药脯氨酸丹参素冰片酯的急性毒性,评价其安全性。方法24只小鼠,雌雄各半,随机分为溶剂对照组和给药组,根据脯氨酸丹参素冰片酯溶液的最大浓度(150 mg·mL^(-1)),单次灌胃,连续观察7 d,记录小鼠毒性反应、体重及饮食饮水量,7 d后小鼠处死,观察主要脏器变化,测定心、肝、肾、肺脏等主要脏器指数,HE染色观察脏器病理性改变。结果实验过程中,脯氨酸丹参素冰片酯给药后小鼠均未出现死亡。与溶剂对照组相比,脯氨酸丹参素冰片酯给药后7 d内,小鼠活动、体重、饮食饮水量均无显著性差异。给药组肝、肾、肺脏指数与对照组相比无显著差异(P>0.05)。与溶剂对照组小鼠相比,雄性小鼠给药组心脏指数无显著差异(P>0.05),而雌性小鼠给药组的心脏指数具有显著降低(P<0.05),且心肌细胞排列紊乱。结论测得脯氨酸丹参素冰片酯对小鼠灌胃的最大耐受量为3000 mg·kg^(-1)。脯氨酸丹参素冰片酯毒性小,安全性较好。Objective To explore the acute toxicity of anti-hypertensive drug proline-Danshensu borneol ester-in mice,and to evaluate its safety.Methods Twenty-four mice were randomly divided into the test group and control group.The maximum tolerated dose(MTD)was determined via single intragastrical administration of the maximal concentration of proline Danshensu borneol ester(150 mg·mL^(-1)).Toxic reactions,body weight and intakes of foods and water were observed for seven consecutive days until the mice were sacrificed.Visceral changes were observed and index of the heart,liver,kidney and lung were recorded.Pathological histology was observed via HE staining.Results There was no death of mice after intragastrical administration of different concentrations of proline Danshensu borneol ester.Compared with the control group,the daily activities,body weight and intakes of foods and water in the test group of mice were not significantly different(P>0.05),so were the indexes of the liver,kidney or lung(P>0.05).The heart indexes of male mice in the test group were not significantly different from those of the control group(P>0.05),but the heart indexes of female mice were significantly decreased(P<0.05)and myocardial cells were disorderly.Conclusion The MTD of proline Danshensu borneol ester in mice is orally 3000 mg·kg^(-1),which leads to low toxicity in mice.

关 键 词：脯氨酸丹参素冰片酯 高血压 急性毒性 半数致死量 最大耐受量 安全性 小鼠 灌胃给药 

分 类 号：R965[医药卫生—药理学]