活络效灵丹颗粒对大鼠的长期毒性试验研究  

Long-term toxicity of Huoluo Xiaoling Dan Granule in rats

作　　者：吴虓飞[1] 高晓新[1] 高阳[1] 胡宇驰[1] 曹春然[1] 

机构地区：[1]北京市药品检验所药物安全评价中心,北京100035

出　　处：《药物评价研究》2016年第6期973-982,共10页Drug Evaluation Research

摘　　要：目的 研究连续ig给予活络效灵丹颗粒对SD大鼠产生的毒性反应.方法 活络效灵丹颗粒高、中、低剂量（以生药计22.75、16.25、9.75 g/kg）连续ig给药26周,整个实验期间观察大鼠的一般状态,测定体质量和摄食量,分别于给药13、26周及停药恢复4周取部分大鼠进行血液学指标、血清生化学指标、脏器系数和组织病理学检查.结果 临床症状观察未见因给药引起的全身毒性反应,但高、中剂量组大鼠在给药中后期体质量增长缓慢,高剂量组大鼠在给药初期摄食量下降;血液学检查中,活络效灵丹颗粒可使血小板（PLT）水平、凝血酶原时间（PT）和活化部分凝血活酶时间（APTT）增高,红细胞分布宽度（RDW）降低,原因与该药活血化瘀作用有关;血清生化学检查中,活络效灵丹颗粒可降低天冬氨酸氨基转移酶（AST）水平,增加血糖（GLU）、总胆红素（TBIL）、碱性磷酸酶（ALP）和总胆固醇（CHO）水平;活络效灵丹颗粒可使肝脏、肾脏和肾上腺系数增高;停药后上述指标均可恢复至正常范围;组织病理学检查未见明显病变.结论 活络效灵丹颗粒（9.75-22.75 9生药/kg）对大鼠长期给药,未见明显毒性反应.Objective To investigate the long-term toxicity reaction ofHuoluo Xiaoling Dan Granule （HLXLD） in SD rats. Methods Rats were randomly divided into four groups： control group; HLXLD low, medium, and high dose （dry herbs： 22.75, 16.25, and 9.75 g/kg） groups, and HLXLD was orally given for 26 weeks. Clinical observation and examination of body weight and food intake were performed during whole experimental stage. The hematology, blood-biochemlcs, organ coefficient, and pathohistology were also examined at 13 weeks and 26 weeks during the administration, and at 4 weeks after the withdrawal, respectively. Results No abnormity was found in all rats in clinical observation, but body weight growth of HLXLD medium and high dose groups was retarded during the mid- and late-stage of administration and the amount of food intake of high dose group decreased at the beginning of the administration. In hematology analysis, HLXLD significantly increased platelet （PLT）, prothrombin time （PT）, and activated partial thromboplastin time （APTT） and significantly decreased red cell distribution width （RDW）, which should be associated with the promoting blood circulation and removing blood stasis effect of HLXLD. In biochemistry analysis, HLXLD significantly decreased aspartate aminotransferase （AST）, increased blood glucose （GLU）, total bilirubin （TBIL）, alkaline phosphatase （ALP）, and total cholesterol （CHO） contents. In addition, HLXLD elevated the coefficient of liver, kidney, and adrenal gland. In histopathological observation, HLXLD showed no apparent influence in organs of rats. No delayed toxicity reaction was showed at four weeks after the administration. Conclusion HLXLD （9.75 to 22.75 g/kg） shows no obvious toxicity in rats for long-term administration.

关 键 词：活络效灵丹颗粒 长期毒性 大鼠 体质量 摄食量 血液学 血清生化 脏器系数 组织病理 

分 类 号：R965[医药卫生—药理学]