CAJ | 학술논문

目的：观察安神补脑液长期灌胃给药对大鼠所产生的毒性反应及严重程度，提供毒副反应的靶器官及其损害的可逆程度，确定无毒反应剂量，以评价安神补脑液长期用药的安全性，为拟定临床试验剂量及观察指标提供参考。方法 Wistar大鼠随机分为安神补脑液低、中、高剂量组（2.5、5、10 mL／kg）和溶剂对照组（灌服同容积蒸馏水2 mL／100 g），每组60只，雌雄各半，每天给药1次，每周给药6 d，连续26周。观察大鼠的外观行为、体重、摄食量，并分别于给药第13、26周末及四周恢复期结束进行血液学及血液生化学等各项指标检测及脏器系数、病理组织学检查。结果长期连续灌胃给予安神补脑液，对动物一般状态、行为活动和外观体征无明显不良影响；各剂量组的摄食量、体重、血液学及血液生化学指标与对照组比较无明显差别；给药3个月、6个月对动物各脏器组织位置、重量和脏器系数无不良影响，但部分脏器重量有所增加，各组动物脏器系数在正常范围内；病理结果显示对照组和安神补脑液高剂量组动物未见明显与给药相关的异常病理改变和毒性改变，恢复期停药后未见延迟性毒性，因此，中、低剂量组动物各脏器组织无需进行组织病理形态学检查。结论安神补脑液长期用药对大鼠未见明确的毒性反应，停药后亦无延迟性毒性反应，预期拟定的临床用药量为安全剂量。
목적：관찰안신보뇌액장기관위급약대대서소산생적독성반응급엄중정도，제공독부반응적파기관급기손해적가역정도，학정무독반응제량，이평개안신보뇌액장기용약적안전성，위의정림상시험제량급관찰지표제공삼고。방법 Wistar대서수궤분위안신보뇌액저、중、고제량조（2.5、5、10 mL／kg）화용제대조조（관복동용적증류수2 mL／100 g），매조60지，자웅각반，매천급약1차，매주급약6 d，련속26주。관찰대서적외관행위、체중、섭식량，병분별우급약제13、26주말급사주회복기결속진행혈액학급혈액생화학등각항지표검측급장기계수、병리조직학검사。결과장기련속관위급여안신보뇌액，대동물일반상태、행위활동화외관체정무명현불량영향；각제량조적섭식량、체중、혈액학급혈액생화학지표여대조조비교무명현차별；급약3개월、6개월대동물각장기조직위치、중량화장기계수무불량영향，단부분장기중량유소증가，각조동물장기계수재정상범위내；병리결과현시대조조화안신보뇌액고제량조동물미견명현여급약상관적이상병리개변화독성개변，회복기정약후미견연지성독성，인차，중、저제량조동물각장기조직무수진행조직병리형태학검사。결론안신보뇌액장기용약대대서미견명학적독성반응，정약후역무연지성독성반응，예기의정적림상용약량위안전제량。
Objective To study the chronic toxicity and its severity of a Chinese medicine, Anshen Bunao Liquid ( ABL) , in rats, provide the target organs and extent of reversibility of their adverse effects, determine its non-toxic dose, and to evaluate the safety of medication and provide reference for clinical trial dose and observation indexes.Methods Two hundred and forty healthy 6-week old Wistar rats ( male:female=1:1) were divided into low,middle, and high dose Anshen Bunao liquid groups (2.5, 5, 10 mL/kg),and solvent control group (distilled water 2 mL/100 g), with 60 rats in each group.The drug was orally administered to rats once a day and 6 days per week for 26 weeks.The general state, body mass and food intake were measured.By the end of 13 weeks, 26 weeks of experiment and 4-week recovery period after drug withdrawal, hematological and biochemical indexes were assayed, organ coefficients were determined, and histopathological observation was performed.Results Long-term continuous oral administration of Anshen Bunao liquid, the general state, behavior and gross appearance showed no significant abnormal changes.Compared with the control group, no significant differences in all checked items were found in the treatment groups.During 3 and 6 months, the size and location of organs,organ weight and organ coefficient had no obvious changes, with only non-significant increase of weight of some organs.All the organ coefficients of the animals in different groups were within normal range.Histopathology showed no obvious patho-logical and toxicological changes even in the high-dose drug treatment group, and no delayed toxicity occurred after with-drawal of drug administration.Conclusions The Chinese drug, Anshen Bunao liquid has no obvious toxicity and no de-layed toxicity after withdrawal of the drug in rats.It is expected that the planned dose in clinical use is a safe dose.