全普CBD油大鼠灌胃长期毒性试验研究  

Chronic Toxicity of the Full-spectrume CBD Oil in Rats

作　　者：唐敏 王振宇[2] 郭翀[3] 项伟 宋京风 TANG Min;WANG Zhen-yu;GUO Chong;XIANG Wei;SONG Jing-feng(School of Pharmaceutical Sciences&Yunnan Provincial Key Laboratory of Pharmacology for Natural Products;Biomedical Engineering Reasearch Center of Kunming Medical University,Kunming Yunnan 650500;the First Affiliated Hospital of Kunming Medical University;Hempson Science and Technology Ltd,Kunming Yunnan 657000;School of Pharmaceutical Sciences&Yunnan Provincial Key Laboratory of Pharmacology for Natural Products of Kunming Medical University,Kunming Yunnan 650500,China)

机构地区：[1]云南省第二人民医院麻醉科,云南昆明650021 [2]昆明医科大学生物医学工程中心,云南昆明650500 [3]昆明医科大学第一附属医院检验科,云南昆明650032 [4]云南省汉木森科技有限公司,云南昆明650500 [5]昆明医科大学药学院暨云南省天然药物药理重点实验室,云南昆明650500

出　　处：《昆明医科大学学报》2020年第10期7-14,共8页Journal of Kunming Medical University

基　　金：云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目[2019FE001(-031)];云南省创新团队项目(202005AE160004)。

摘　　要：目的观察全普大麻二酚(Cannabidiol,CBD)油连续重复给予SD大鼠的毒性反应,为拟定临床人用安全剂量提供参考。方法 150只SD大鼠,随机分为五组,每组30只,设溶媒对照组(玉米油),阴性对照组(高压灭菌水)和全普CBD油低(50 mg/kg)、中(125 mg/kg)、高(250 mg/kg)三个剂量组,按5 m L/kg灌胃给药,相当于成人临床用药量的10、25、50倍,同时分别给予等容量玉米油和高压灭菌水作为溶媒和阴性对照。每天给药观察,记录临床症状和死亡情况。每周称体重、摄食量,给药13周和恢复4周解剖,进行血液学、血清生化、脏器系数、脏脑系数及病理学检查。结果全普CBD油可使大鼠耗食量减少;给药高、中剂量组血清谷丙转氨酶(ALT)升高(P<0.01),血清碱性磷酸酶(ALP)升高(P<0.01),血清白蛋白(ALB)降低(P<0.01),且存在明显的剂量-反应关系;组织病理学检查高、中剂量组可见肝细胞脂肪变性,且肝脏重量及系数升高。结论全普CBD油经口长期给药的安全剂量为50 mg/kg,相当于人体拟推荐用量的10倍以下为安全剂量。临床用药应重点关注肝脏功能的变化。Objective To investigate the chronic toxicity of the full-spectrume CBD oil. Methods 150 healthy SD rats were randomly divided into five groups with 30 rats in each group. The solvent control group(corn oil), the negative control group(high pressure sterilized water) and the low(50 mg/kg), medium(125 mg/kg)and high(250 mg/kg) group of CBD oil were set up and the administration was given by gavage at the dose of 5 m L/kg, which was equivalent to 10, 25 and 50 times of the clinical dosage of adults. At the same time, the equal volume of corn oil and high-pressure sterilized water were used as the solvent and negative control respectively. General observation was conducted, and clinical signs and mortality were recorded daily.Besides, the rats were weekly weighed and their food consumptions were also recorded.On 13 weeks and the recovery period, the rats were dissected to conduct hematology, serum biochemistry, organ index and pathological examination.Results The full-spectrume CBD oil induced the food consumption of rats. Long-term high and medium-dose administration led to the increase of glutamate pyruvic transaminase( ALT), alkaline phosphatase( ALP),induced Serum albumin(ALB). Besides,it also raised the weights and ratios of liver.There was a significant dose-response relationship. Additionally, pathological examination occasionally observed steatosis. Conclusion This study demonstrates that the safe dose for long-term oral administration of the full-spectrume CBD oil is 50 mg/kg. A safe dose is less than 10 times the recommended human dose. The results indicate that we should pay more attention to the changes in liver function in clinical drug use.

关 键 词：全普CBD油 大鼠 长期毒性试验 肝毒性 

分 类 号：R99[医药卫生—毒理学]