消癌舒胶囊急性毒性及长期毒性的实验研究

Experimental study on the acute and long-term toxicity of Xiao Ai Shu capsules in rats

目的研究消癌舒胶囊的急性毒性及长期毒性。方法雌性KM小鼠40只,随机分成4组,消癌舒给药剂量为2.36、2.94、3.68、4.6 g/kg,单次灌胃给药,每次0.2 mL/10 g,观察小鼠一般情况及中毒、死亡情况,连续观察14 d,测定半数致死量(LD50);雌性KM小鼠20只,消癌舒给药剂量为27.6 g/kg,分3次灌胃给药,给药容积0.4 mL/10 g,观察小鼠的一般情况及中毒反应,连续观察14 d,计算小鼠消癌舒的最大耐受量倍数;120只雌性SD大鼠随机分为4组(30只/组):消癌舒低、中、高剂量组(1、2.3、4.6 g/kg)及空白对照组,每日灌胃给药1次,每周测1次体重和摄食量,分别于给药3、6个月及停药1个月(恢复期)后,每组随机处死10只动物,并检测血液学、血清生化、脏器系数及各组织病理学指标。结果急性毒性实验显示消癌舒各组小鼠实验期间未见死亡,一般情况良好,不能求出LD50,小鼠的最大耐受量是人用量的375倍;长期毒性实验显示消癌舒给药3个月大鼠体重和摄食量均有降低(P<0.01),给药6个月大鼠摄食量降低(P<0.05),停药1个月均恢复正常;消癌舒给药3个月,给药组红细胞(RBC)、血红蛋白(HGB)、红细胞压积(HCT)、平均红细胞血红蛋白浓度(MCHC)、血小板(PLT)增加,与对照组比较差异有统计学意义(P<0.05或P<0.01),其它血液学及血清生化指标未见异常,连续给药6个月,给药组中性粒细胞百分比(NEUT)、尿素氮(UREA)、血糖(GLU)增加,淋巴细胞百分比(LYMPH)、总蛋白(TP)、白蛋白(ALB)降低,与对照组比较差异有统计学意义(P<0.05或P<0.01),其它血液学及血清生化指标未见异常,消癌舒停药1个月血液学及血清生化指标均恢复正常;给药3、6个月及恢复期消癌舒各剂量组大鼠的心、肝、脾、肺、肾、脑、卵巢、子宫等脏器系数及其组织形态学均未见明显异常。结论消癌舒胶囊无明显急性毒性及长期用药毒性反应,临床用药量安全。

Objective To study the acute toxicity and long-term toxicity of Xiao Ai Shu(XAS).Methods 40 female KM mice were randomly divided into four groups,and XAS was administered by single gavage at 2.36,2.94,3.68 and 4.6 g/kg,0.2 ml/10 g each time.The general conditions of the mice as well as their poisoning and deaths were observed,and the LD50 was determined after 14 consecutive days of observation;20 female KM mice were administered with a dose of 27.6 g/kg by gavage at 3 times,with a volume of 0.4 ml/10 g.The general conditions and toxic reaction of the mice were observed,and the maximum tolerance multiple of XAS was calculated after continuous observation for 14 days.120 female SD rats were randomly divided into four groups,with 30 rats in each group.The groups were:low,medium,and high dose groups(receiving 1,2.3,and 4.6 g/kg of the drug,respectively),and a blank control group.The drug was administered via gavage once daily.Body weight and food intake were measured weekly.After 3 and 6 months of treatment,as well as one month after drug discontinuation(recovery period),10 rats from each group were sacrificed to assess hematological,serum biochemical,and organ coefficient markers,and various histopathological indexes.Results Acute toxicity experiments showed that there was no death during the experimental period in all groups of mice,the general condition was good,the LD50 could not be calculated,and the maximum tolerated dose of mice was 375 times of the human dose;long-term toxicity experiments showed that the body weight and food intake of the rats decreased after 3 months(P<0.01)of XAS administration,and its administration for 6 months led toless food intake(P<0.05)which returned to normal one month after withdrawal of the drug;after 3 months of administration,RBC,HGB,HCT,MCHC,PLT increased in the administered group,which was statistically significant compared with the control group(P<0.05 or P<0.01),and no abnormalities were found in other hematological and serum biochemical indices.After 6 months of continuous administration,NEUT,UREA,GLU increased,and the percentage of LYMPH,TP,ALB decreased in the drug-dosing group,which was statistically significant compared with the control group(P<0.05 or P<0.01),and no abnormality was found in the other hematological and serum biochemical indexes.All the hematological and serum biochemical indexes returned to normal after withdrawl of XAS for a month.The coefficients of heart,liver,spleen,lung,kidney,brain,ovary,uterus and other organs and their histomorphology of the rats in the dosage groups of XAS were not obviously abnormal in the administration of the drug at 3,6 months and the recovery period.Conclusion There is no obvious acute toxicity and long-term drug toxicity reaction for XAS consumption,and the clinical dosage of the drug is safe.