摘要
目的 观察桂芍子喘方(GSZC)单次给药及重复给药26周对SD大鼠的毒性反应,为临床研究和安全用药提供参考。方法 单次给药毒性试验:SD大鼠按体重随机分为对照组和给药组(GSZC),给药组给予最大药物浓度0.47 g(药粉)·mL^(-1),给药体积2 mL·100 g^(-1),给药剂量139.12 g(生药)·kg^(-1),24 h内给药2次,对照组给予等体积饮用纯净水。观察最大给药量单次灌胃SD大鼠毒性反应,并持续观察14天,评价指标包括毒性症状、体重、饲料消耗量及组织病理学检查。重复给药毒性实验:SD大鼠随机分为4组,设GSZC高、中、低剂量组[65.1、32.6、16.3g(生药)·kg^(-1)]及对照组。每日上午灌胃给药1次,给药体积2 mL·100g^(-1),连续给药26周,停药后恢复期4周。检测指标包括一般情况、动物体重、饲料消耗量、血常规、生化、凝血指标,脏器系数和病理组织学检查等。结果 单次给药实验中,SD大鼠灌胃给予GSZC,最大耐受剂量>139.12 g(生药)·kg^(-1),相当于临床拟用剂量85.17倍,未见明显毒性;重复给药实验中,SD大鼠灌胃给予GSZC重复给药26周,无毒反应剂量为16.3 g(生药)·kg^(-1),相当于临床拟用剂量的10倍。长期给予GSZC可能引起动物血液检测指标的可逆性改变,临床用药时应加强相关指标监测。结论 GSZC对SD大鼠在拟临床使用剂量范围及疗程内未见明显的毒性反应。
Objective To investigate the toxicity of Guishaozichuan granules(GSZC)in SD rats following single-dose and 26-week repeated-dose administration in order to provide a reference for clinical safety evaluation and adverse reaction monitoring.Methods Single-dose toxicity study:Rats were randomized into control and GSZC groups.The GSZC group received the maximum feasible dose(0.47 g herbal powder·mL^(-1),2 mL·100 g^(-1),total dose 139.12 g(herbal medicine)·kg^(-1))via oral gavage twice within 24 h,while controls received an equivalent volume of purified water.Toxicity symptoms,body weight,feed consumption,and histopathology were monitored for 14 days.Repeated-dose toxicity study:Rats were divided into control and GSZC high-,medium-,and low-dose groups(2 mL·100 g^(-1))that were subjected to 26 weeks of continuous administration followed by a 4-week recovery period.Parameters for detection included clinical observations,body weight,hematological,biochemical,and coagulation parameters,organ coefficients,and histopathology.Results Single-dose study:The maximum tolerated dose exceeded 139.12 g·kg^(-1) with no significant toxicity.Repeated-dose study:The no-observedadverse-effect level was 16.3 g·kg^(-1).Reversible alterations in hematological/biochemical parameters were observed at higher doses,warranting clinical monitoring.Conclusion GSZC may demonstrate no significant toxicities at clinically adopted doses and within the course of treatment in SD rats.
作者
张慧婷
李友林
李磊
阎玥
姚婷
李春雷
史琦
ZHANG Huiting;LI Youlin;LI Lei;YAN Yue;YAO Ting;LI Chunlei;SHI Qi(Graduate School,Beijing University of Chinese Medicine,Beijing 100029,China;Department of Integrated TCM and Western Medicine for Pulmonary Diseases,China-Japan Friendship Hospital,Beijing 100029,China;Respiratory Disease Center,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)
出处
《中国药物警戒》
2025年第5期547-553,569,共8页
Chinese Journal of Pharmacovigilance
基金
中央高水平医院临床科研业务费(2024-NHLHCRF-PYI-08)
国家自然科学基金资助项目(82305155、81904184)
北京市科学技术委员会“十病十药”研发项目(Z161100001816004)。
作者简介
张慧婷,女,博士,中西医结合防治哮喘等呼吸疾病的临床与机制研究;通信作者:史琦,女,副主任医师,博士,中西医结合防治肺系及过敏性疾病的临床与基础研究。E-mail:Shiqi19830910@163.com。
