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目的观察静脉注射ZSY 90 d为临床安全用药提供参考。方法选用SD大鼠120只,雌、雄各半,设溶剂对照组和ZSY 10,20和40μg·kg-1,静脉注射给药,连续给药90 d。给药体积0.2 m.l100 g-1。给药结束(d 91)剖杀每组每性别10只动物,停药30 d(d 121)后,剖杀每组每性别5只动物。检测指标包括动物一般状况、体重、摄食量、血液常规、血清生化、尿常规和病理组织学检查等。结果在本试验条件下,实验期间动物外观无异常,行为活动正常,粪便颜色、形状正常。试验期间雌鼠和雄鼠低剂量体重与对照组比较无显著性差异;雄鼠中、高剂量组体重和对照组比较分别于给药d 50～90和d 29～90出现了显著性差异,体重分别低于对照组7.12%～9.21%、6.31%～10.30%,恢复期体重和对照组比较无显著性差异。给药期间,各给药组摄食量、血液学、血清生化、电解质、凝血及脏器重量及系数这些指标未见与受试物明显相关的毒性反应。各给药组动物与对照组比较,脏器组织未发现与给药明确相关的毒性病理改变。停药30 d后,与对照组比较,除高剂量组动物注射部位纤维结缔组织增生发生率略高外,各给药组动物脏器组织未发现延迟或蓄积毒性病理改变。结论在本实验室条件下,未见血液、生化、病理等指标出现与给药相关改变。本研究中未见明显毒性反应剂量雌鼠为40μg·kg-1,雄鼠为10μg·kg-1。
Objective To observe the 90-day intravenous injection of ZSY for clinical safety drugs provide a reference. Methods 120 Sprague-Dawley rats were randomly divided into male and female male Sprague-Dawley rats. The rats in the control group and ZSY 10, 20 and 40 μg · kg-1 were injected intravenously for 90 days. Administration volume 0.2 m.l100 g-1. At the end of dosing, 10 animals per gender were sacrificed and animals were sacrificed for 30 d (d 121) and 5 animals per gender were sacrificed. Test indicators include the general status of animals, body weight, food intake, blood routine, serum biochemical, urinalysis and histopathological examination. Results Under the experimental conditions, the appearance of animals during the experiment was normal, the behavior was normal, and the color and shape of the feces were normal. There was no significant difference between low dose body weight of the female and male rats during the experiment and the control group. The body weight of the middle and high dose groups of the male rats was significantly different from that of the control group on d 50-90 and d 29-90, Respectively, lower than the control group 7.12% ~ 9.21%, 6.31% ~ 10.30%, body weight recovery and no significant difference between the control group. During the administration, there was no toxic reaction obviously associated with the test substance on the indexes of food intake, hematology, serum biochemical, electrolyte, coagulation and organ weight and coefficient of each administration group. Compared with the control group, no obvious pathological changes were found in visceral tissues and the administration groups. After 30 days of drug withdrawal, compared with the control group, except for the high-dose group, the incidence of fibrous connective tissue hyperplasia was slightly higher at the injection site of animals, and no delay or accumulation of toxicological pathology was found in the organs and tissues of each administration group. Conclusion No changes of blood, biochemistry and pathology were found in the laboratory under the conditions of administration. In this study, no obvious toxic reaction dose of 40μg · kg-1 female rats, male rats 10μg · kg-1.