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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 m L/kg)和溶剂对照组(灌服同容积蒸馏水2 m L/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。
Objective To observe the toxic reaction and severity of Anshen Bunao liquid administered by long-term gavage to rats, provide target organs with toxic side effects and the reversible degree of damage, and determine the dose of non-toxic reaction to evaluate the effect of Anshen Bunao fluid Medication safety, to develop clinical trials dose and observation indicators provide a reference. Methods Wistar rats were randomly divided into low, middle and high dosage groups (2.5, 5, 10 m L / kg) and solvent control group (2 mL / 100 g distilled water) Only, male and female, administered once a day, weekly dosing 6 d, for 26 weeks. The appearance behavior, body weight and food intake of the rats were observed. At the end of the 13th and 26th week of the administration and the convalescence of the four weeks, the indexes of hematology and blood biochemistry, organ coefficient and histopathological examination were observed. The results of continuous gavage given soothe the Bunao solution, the general state of animals, behavioral activities and appearance of signs no significant adverse effects; each dose of food intake, body weight, hematology and blood biochemical indicators compared with the control group no significant difference; Administration of 3 months and 6 months had no adverse effect on the tissue location, weight and organ coefficient of animals, but the weight of some organs increased and the organ coefficient of each group was within the normal range. The pathological results showed that the control There were no obvious pathological changes and toxicity changes in the high-dose group of Amniotic fluid and soothing the brain-nourishing liquid, and no delay-induced toxicity was found after the withdrawal in the convalescent period, therefore, the organs of middle and low dose groups did not need to be carried out Histopathological examination. Conclusion There is no clear toxic reaction in rats after long-term administration of Anshen Bunao Solution, and there is no delayed toxic reaction after withdrawal. The expected clinical dosage is safe dose.