关键词: 牛蒡子苷元, 皮下注射, Beagle犬, 长期毒性

Abstract: Objective To observe the toxicity of arctigenin in Beagle dogs by continuous subcutaneous injection, so as to provide reference information for the clinical research. Methods 40 healthy conventional Beagle dogs, half male and half female, were divided into 5 groups: control group, polyethylene glycol (PEG) control group and arctigenin (NBZGY) 6, 20, 60 mg·kg^-1 groups, 8 dogs in each group. Dogs of each group were given 1.2 mL·kg^-1 by subcutaneous injection 1 time per day for 28 days, and observed for 2 weeks after the last administration. During the experiment, the general state of animals, food consumption, body weight, hematology, blood biochemistry parameters were detected. Results The stimulus response caused by PEG had been seen in the administration location of PEG-control group and NBZGY each dose group, 60 mg·kg^-1 NBZGY group could strengthen the stimulation, after the last administration, the stimulus response could be partly recovered. 20 and 60 mg·kg^-1 induced injury of liver and biliary duct in contrast to the control group during the period of administration. At the end of convalescence, dogs in 20 mg·kg^-1 group showed a recovery of the injury of liver and biliary duct, but the injury of liver and the biliary duct had not recovered obviously in the 60 mg·kg^-1 group. There was no overt toxicity in 60 mg·kg^-1 group except the stimulus response in the administration location. Conclusion Repeated subcutaneous injection of large dose of NBZGY can induce injury of liver and biliary duct and strengthen the reaction to the stimulus caused by PEG in dogs.

Key words: arctigenin, subcutaneous injection, Beagle dog, repeated dose toxicity