通脉活血灵胶囊的毒理学研究

目的观察小鼠和大鼠口服通脉活血灵胶囊的急性毒性和长期毒性作用。方法采用最大给药量法测定小鼠口服通脉活血灵胶囊的最大耐受量;采用3个剂量(9.0,4.5,1.5 g/kg)iq SD大鼠,连续180 d,观察给药90,180 d时大鼠的生长发育、血液学、血液生化学、组织病理变化及停药30 d时上述指标的变化。结果小鼠口服通脉活血灵胶囊的最大耐受量为36.0 g/kg。大鼠连续给药90 d时,9.0 g/kg肌酐比空白对照组升高(P<0.01);肾重量系数增高(P<0.01);2只大鼠肾脏近曲小管上皮细胞高度水肿,轻度脂肪变性,管腔变大,肾小管内可见红细胞管型,肾间质少量炎细胞浸润;2只大鼠肝细胞脂肪变性。给药180 d时,9.0 g/kg和4.5 g/kg剂量组肌酐升高(P<0.01或P<0.001);9.0 g/kg剂量组总蛋白升高(P<0.01);肝、肾脏系数增高(P<0.01);3只大鼠肾脏近曲小管上皮细胞高度水肿,轻度脂肪变性,管腔变大,肾间质少量炎细胞浸润。2只大鼠肝细胞轻度脂肪变性;停药30 d后,大鼠体重、摄食量、活动、外周血象、重要器官脏器系数均正常,病理学检查各组各脏器均未发现明显改变。结论通过对通脉活血灵胶囊180 d用药过程中各项指标反应的观察认为,通脉活血灵胶囊在规定剂量下服用是安全可靠的。

Toxicologic Study on Tongmai-huoxueling Capsule

Objective To observe the acute toxicity in mice and the long-period toxicity Tongmaihuoxueling Capsule(TMHXL) in rats.Methodsthe maximum administration dosage(MAD) of TMHXL were determined by iq administration in mice.Body weight,hematological and hematobiochemical parameters,coefficient and histomorphological figure of organs(the heart,liver,spleen,lungs,kidneys,adrenals,testes,prostate,paucreas,uterus,brain,thymus) were examined in 90 days,180 days and 30 days after the cessation of TMHXL.ResultsThe MAD of TMHXL by iq administration was greater than 36.0g/kg in mice.In the long-period toxicity test,after administered repeatedly for 90 days,in 9.0g/kg dose group,Crea increased(P<0.01);the epithelium cells edema of proximal convoluted tubule and fat degened,lumens broadend in two,the fat in liver cells were degenerated in two rats.After administerd repeatedly for 180 days,in the 9.0 g/kg dose groups,the TP and Crea increased(P<(0.01)orP<0.05);The weight coefficients of kidneys and liver were larger in high dose group than that of in control group;the epithelium cells edema of proximal convoluted tubule and fat degened,lumens broadend in three;the fat in liver cells were degenerated in two rats.In the 4.5 g/kg dose groups the Crea increased(P<0.05).In 30 days after stopping the drug,the changes of Crea,TP,hematobiochemical,pathological and coefficient of organs could completely recover.ConclusionIt could be concluded that TMHXL is safe to be administrated in the dose prescribed.