摘要
Wang Shi Bao Chi Wan(WSBCW)is a traditional Chinese medicine with a recorded administration history of more than 180 years.In the present study,the preclinical safety of WSBCW was evaluated the preclinical safety of WSBCW using a toxicity test,which consisted of an administration period of 28 d and a recovery period of 15 d.During the test,male and female SD rats were administered the medicine once a day by oral gavage,at a dose of 60 mg/kg/day,600 mg/kg/day,or 1500 mg/kg/day.As a reference medicine,mosapride citrate was administered at a dose of 37.5 mg/kg/day,which was clinically equivalent to the high-dosage treatment of WSBCW.With all the dosage groups,statistically,no adverse effect was observed in terms of clinical observation,food intake,body weights,organ coefficient,blood biochemistry,and histopathology examination.No intestinal melanosis was observed in the rats.When the data were examined animal by animal,test substance-related adverse effects were found with the high-dosage rats in hematology assay.The deranged,however,reversible changes suggested a compromised intestinal barrier,which was also observed with in mosapride citrate-treated rats.In addition to the histopathology assay,molecular toxicology was explored using high-throughput gene sequencing.No evident toxicity was revealed.In summary,administration of WSBCW was well tolerated within a treatment of 28 d.
王氏保赤丸是一个具有180多年应用历史的中药复方。本研究利用大鼠给药模型,对王氏保赤丸的临床前安全性进行了研究。在28天的给药实验期间,对SD大鼠进行每日1次的灌胃给药,对高、中、低剂量组而言,给药剂量分别为60 mg/kg/day、600 mg/kg/day和1500 mg/kg/day。给药结束后,进行15天的恢复期观察。以枸橼酸莫沙必利为参照药物,给药剂量为37.5 mg/kg/day,与王氏保赤丸的高剂量组保持一致。各剂量组在临床观察、摄食量、体重、脏器系数、血液生化、组织病理学等方面均未见不良反应,并且也未见肠黑变现象的发生。在血液学实验中,发现王氏保赤丸高剂量组的某些大鼠的血常规指标出现异常变化,但在恢复期后基本回归正常,这种可逆性的影响可能源于受损的大鼠肠道屏障。同时,我们在枸橼酸莫沙必利给药组中也观察到了这一现象。除常规的组织病理学检测外,我们还利用高通量基因测序技术进行了研究,也未发现对细胞通路明显的毒性作用。综上所述,实验动物在28天的给药期内,对王氏保赤丸具有良好的耐受性。
作者
Tao Gao
Lei Liu
Yan Wu
Quan Du
高涛;刘蕾;吴燕;杜权(北京大学药学院天然及仿生药物国家重点实验室,北京100191;北京医院药学部国家老年医学中心中国医学科学院老年医学研究院,北京100730;中国人民解放军空军特色医学中心药剂科,北京100142)
基金
Beijing Municipal science&Technology Commission(Grant No.2161100001816008)
the National Natural Science Foundation of China(Grant No.31571403)
Beijing Natural Science Foundation(Grant No.2171001)。
