同仁安神丸的安全性评价

Safety of Tongren Anshen Pill

目的：通过对同仁安神丸长期用药的安全性评价,明确其潜在的毒性作用及可逆性、毒性靶器官、无不良作用剂量及用药时间,为临床安全用药提供依据。方法：SD大鼠随机分为4组,正常组（每日灌胃给予饮用水）和同仁安神丸高、中、低剂量组（含生药6.4,3.2,1.6 g·kg^-1）。每日灌胃1次,连续给药3个月。分别于给药1,3个月和停药2个月后解剖并分析血液生化、血液细胞、尿常规、脏器系数和组织形态学等指标。结果：给药1个月,除高剂量组体重降低、饲料消耗量减少外,血液细胞、生化、尿常规、脏器系数等指标及脏器组织病理学检查等均未见明显与毒性相关的变化。给药3个月,高剂量组雌性动物的天门冬氨酸氨基转换酶（AST）,肌酸激酶（CK）较正常组显著增高;病理检查可见肝细胞、肾小管轻度变性和肾间质炎性浸润等病理变化,其他血液生化学指标及血液学、尿常规、脏器系数等指标均在该品系动物的正常值范围内,故不认为有毒性学意义。停药2个月后,高剂量组上述肝功能指标和肝、肾组织形态学基本恢复正常。结论：高剂量组大鼠长期给药时,可见轻度肝肾毒性损伤。给予同仁安神丸3个月的无明显不良作用剂量（NOAEL）为3.2 g·kg^-1·d-1,相当于临床剂量的29倍。临床上服用该药时,应严格控制剂量,服药时间不宜过长。

Objective： To define potential toxicity and reversibility,target organs of toxicity,no adverse effect dosage and medication time of Tongren Anshen pill through the safety evaluation for long-term medication of Tongren Anshen pill,in order to provide basis for clinical safety medication. Method： SD rats were randomly divided into four groups： the control group and high-dose,medium-dose and low-dose Tongren Anshen pill groups（ containing 6. 4,3. 2,1. 6 g·kg^-1 of medicinal herbs）. The rats were administered with the drugs by gavage once daily for 3 months. The blood biochemistry, hematology, urinalysis, relative organ weights（ ROWs） and histomorphological indexes were examined in the 1 stand 3 rdmonths after administration,and the 2 ndmonth after drug discontinuance. Result： In the study,the results of hematology,biochemistry,urinalysis,ROWs and histopathological examination showed no significant change related to drug toxicity after 1 month of administration;however,the body weights and food consumption of rats in high-dose Tongren Anshen pill group were significantly decreased. After 3 months of administration,aspartate aminotransferase（ AST） and creatine kinase（ CK） of female rats in the high-dose group significantly increased compared with those in the control group. The histopathological changes in livers and kidneys were observed, including hepatocytes, mild renal tubular degeneration and renal interstitial inflammatory infiltration. There were no significant difference in other indexes,including serum biochemistry,hematology,urinalysis and ROWs. Two months later after drug discontinuance,no significant change in liver function parameters and morphology of liver and kidney was observed in the high-dose group. Conclusion： Long-term administration with high-dose Tongren Anshen pill could induce slight hepatic and renal damages. No observed adverse effect level（ NOAEL） is 3. 2 g·kg^-1·d-1,which was equivalent to 29 times of clinical dosage. Its dosage and medication time shall be strictly controlled in clinic.