骨宝口服液大鼠长期毒性实验结果分析

Study on Long-term Toxicity of Gubao Oral Solution

目的通过动物长期试验研究骨宝口服液的安全性,为临床用药安全提供科学依据。方法 2016-03/2017-03选用SD大鼠,骨宝口服液按19.00、9.52、5.4 g浸膏/kg体重(相当于72、36和20 g药材/kg体重)3个剂量,分别相当于成人临床最大日用量的70、35和20倍,连续对大鼠灌胃给药6个月及恢复期。给药期间每日观察大鼠一般体征状况,每周测定体重变化,给药3个月、6个月及恢复期处死部分动物,测定血液学和血液生化指标,并做组织病理学检查。结果在给药初期部分动物出现溏便、竖毛现象,3周后恢复;给药期间部分动物摄食量减少(P<0.001、P<0.01或P<0.05),体重减轻(P<0.05);长期给予高剂量RBC、HGB、AST、T-Bil、Glu、TG值降低(P<0.05)、PT值升高(P<0.05),停药期间K、Na、Cl升高(P<0.05);雌性组肺指数增高(P<0.05)。长期给予中剂量RBC、HCT、WBC、LYM、AST、T-Bil、Glu、CK值降低(P<0.05),雌性组心、肺、肾、胸腺指数增高(P<0.05),雄性组脾指数降低(P<0.05)。长期给予低剂量ALT、AST、CK值降低(P<0.05),PT值升高(P<0.05),胸腺指数升高(P<0.05);病理学检查,未见与药物相关的明显病变,停药后也未见药物延迟性毒性反应。结论在本试验条件下,骨宝口服液长期用药,对大鼠部分血液学、肝功能、电解质指标,及心、肺、肝、肾脏器指数有一定的影响。试验提示本品长期用药的安全剂量为20 g药材/kg以下。

Objective To study the long-term toxicity of gubao oral solution in rats after intragastric administratin,so as to provide reference for clinical drug practice safety.Methods SD rats were given gubao oral solution from March 2016 to March 2017,and divided into three doses of 19.00 g,9.52 g and 5.4 g extract/kg(equivalent to 72 g,36 g and 20 g medicinal herbs/kg),which were respectively 70,35 and 20 times higher than the maximum daily adult clinical dosage.The rats were given oral administration for 6 months and 1 month of recovery period.General information of rats was observed,the body weight of rats were measured once a week.At the 90 st day of administration,180 st day of administration and the end of recovery period,10,20 and 10 rats were killed from each group to observe their hematology,blood biochemistry,organ coefficient and histopathology changes.Results At the early stage of drug administration,some animals showed signs of loose bowels and piloerection,which recovered after 3 weeks.During the administration period,some rats’food intake decreased(P<0.05)and got weight loss(P<0.05).Long-term high-dose group showed decrease in RBC,HGB,AST,T-Bil,Glu,and TG(P<0.05),while showed increase in PT(P<0.05),and K,Na,and Cl increased during withdrawal(P<0.05),lung index of the female group increased(P<0.05).After long-term administration of medium-dose,the rats’RBC,HCT,WBC,LYM,AST,T-Bil,Glu,and CK values decreased(P<0.05),and the heart,lung,kidney,and thymus indexes of female groups increased(P<0.05),the spleen index of the male group decreased(P<0.05).For the long-term administration of low-dose,the rats’ALT,AST,and CK values decreased(P<0.05),PT values increased(P<0.05),and thymus index increased(P<0.05).Pathological examination indicated no obvious drug-related lesions and no delayed drug toxicity after drug withdrawal.Conclusion Under this test condition,the long-term use of gubao oral solution had a certain impact on hematology,liver function,electrolyte indexes,and heart,lung,liver and kidney organ indexes of rats.The test indicated that the safe dose for long-term use of this medicine was less than 20 g medicinal materials/kg.