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目的AF-5/PVP固体分散体对机体产生的中毒反应研究及其严重程度、主要毒性靶器官以及损害的可逆程度。方法设10、50和250mg/kg,PVP对照组及一个蒸馏水对照组。以每周给药6次,15ml/kg体积给Wistar大鼠灌胃给药共6个月和停药恢复期3周毒性研究。结果对动物的一般活动状况、粪便、饮食和饮水等未发现受影响;对动物体重也无明显的影响,但在250mg/kg剂量水平有抑制动物体重增长的趋势;250mg/kg剂量水平引起动物尿生化指标阳性增加的改变在停药后能够恢复正常;对动物的神经活动状况未见明显影响;血液学:6个月时出现AF-5/PVP固体分散体相关的中性粒细胞比例增加,淋巴细胞比例降低;血清生化:出现剂量相关的ALT增加,ALP降低;脏器重量:出现剂量相关的肝脏、肾脏重量的增加;组织病理学:250mg/kg剂量的雌性动物(8/10)动物和雄性动物(8/9)动物均发现有极轻度的肝小叶中心性肝细胞肥大。结论主要毒性靶器官是肝脏、肾脏;无明显毒副反应的剂量是50mg/kg;停药3周后,给药引起的肝脏、肾脏毒性反应能够恢复。
Objective To study the toxic effects of AF-5 / PVP solid dispersions on the body and their severity, the main toxic target organs and the degree of reversibility of the damage. Methods 10, 50 and 250mg / kg, PVP control group and a distilled water control group. The rats were administered 6 times a week, 15 ml / kg volume to the Wistar rats for 6 months, and the drug withdrawal recovery period of 3 weeks toxicity study. Results The animals were not affected by general activities, feces, diet and drinking water, and had no significant effect on the body weight of animals. However, there was a tendency of inhibiting body weight gain at the 250mg / kg dose level. The 250mg / kg dose level caused the animals Changes in positive biochemical markers of urine returned to normal after discontinuation; no significant effect on neurological activity in animals; hematology: increased proportion of neutrophils associated with solid dispersion of AF-5 / PVP at 6 months , The proportion of lymphocytes decreased; serum biochemistry: increased dose-related ALT, decreased ALP; organ weight: dose-related increase in liver and kidney weight; histopathology: female animals at a dose of 250 mg / Animals and male animals (8/9) animals were found to have very mild hepatic lobule central hepatocyte hypertrophy. Conclusion The main toxic target organs are liver and kidney. The dose of no obvious side effects is 50 mg / kg. After 3 weeks’ withdrawal, the toxic reactions of liver and kidney can be recovered.