目的 观察Beagle犬连续口服曼陀罗子提取物(MTL)的长期毒性反应.方法 Beagle犬24只,随机分为空白对照组及低、中、高剂量药物组,每组6只.低、中、高剂量药物组分别给予MTL 40,80,160 mg·kg-1·d-1,po,qd,连续3个月,空白对照组给予羧甲基纤维素钠.末次给药24 h每组处死4只犬,停药后恢复2周每组再处死2只犬,分别检测血液学、血液生化学等指标,测定脏器系数,进行系统尸检、脏器组织病理学检查.结果 中、高剂量药物组犬给药后出现活动先增多后减少、扩瞳、口干、呕吐等症状;与空白对照组比较,中、高剂量药物组犬体质量明显降低,血小板计数、淋巴细胞数目、肌酸磷酸激酶明显升高,粒细胞数目明显降低;组织病理学检查无明显变化.结论 MTL连续口服给予Beagle犬 3个月,对犬中枢神经系统、消化系统、血液系统、心脏有一定毒性.MTL对Beagle犬安全剂量不高于40 mg·kg-1·d-1(相当于生药388 mg·kg-1·d-1).%Objective To investigate the chronic toxicology of Datura stramonium L.( MTL ) extract in Beagle dogs.Methods 24 health Beagle dogs were randomly divided into low,middle and high dose groups, which were treated with MTL extract ( 40,80,160 mg · kg-1 · d-1 ) by oral administration, respectively, once a day for 3 months.The blank control dogs were treated with carboxymethyl cellulose sodium.Four dogs in each group were killed 24 h after the last treatment, and two dogs in each group were killed 2 weeks after treatment withdrawal.The hematology and biochemical indexes and organ coefficients were detected.The systematic postmortem and organ histopathology were examined.Results Some symptoms like pupil dilation,dry mouth and emesis appeared in the high and middle dose of MTL treated dogs compared with the controls; the weight loss of dogs in the middle and high dose groups were reduced significantly; platelet count/blood platelet count ( PLT ), lymphoid cells ( LYMPH ) and creatine kinase ( CK ) increased significantly, granulocytes ( GRAN ) decreased obviously; there was no significant change in organ histopathology.Conclusion MTL extract by oral administration for consecutive 3 months has a certain chronic toxicity on the central nervous system, digestive system, blood system and heart.The safety dose of MTL extract for Beagle dogs is not above 40 mg· kg-1 · d-1( crude drug 388 mg· kg-1 · d-1 ).
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