血脂宁丸对正常大鼠长期毒性实验研究

Chronic Toxicity of Xuezhining Pill on Normal Rats

目的观察血脂宁丸对正常大鼠毒性有无、主要表现、受累脏器及停药后的恢复情况,为临床安全用药提供毒理学依据。方法参照《中药、天然药物长期毒性研究技术指导原则》进行试验,观察大鼠连续给药90 d及停药45 d后大鼠体重、日饮食量、日饮水量变化等一般状况的变化,末次药后24 h各组随机选取10只大鼠心脏取血,进行血液学指标及血生化指标检测;大鼠取血后处死解剖,剖取心、肝、脾、肺、肾、肾上腺、胸腺、子宫、卵巢、脑、胃、小肠、胸腺、附睾、结肠、直肠等脏器,观察其大小、颜色、硬度等外观形状变化,除肠管以外所有脏器均计算其脏脑比值,并将所取脏器进行常规病理组织学检查。结果实验过程中,各组大鼠均未出现死亡。连续给药90 d,与正常组比较,各组大鼠体重增长缓慢(P>0.05);高剂量组红细胞平均体积(MCV)、网织红细胞(RET)极显著降低(P<0.001),红细胞比容(HCT)、凝血酶原时间(PT)显著降低(P<0.01),红细胞平均血红蛋白量(MCH)显著升高(P<0.01);中剂量组MCH显著升高(P<0.01),RET显著降低(P<0.01);高剂量组丙氨酸氨基转移酶(ALT)、碱性磷酸酶(ALP)极显著升高(P<0.001),甘油三酯(TG)极显著降低(P<0.001),天冬氨酸氨基转移酶(AST)、血尿素氮(BUN)、肌酐(Cr)、白蛋白(ALB)显著升高(P<0.01),总胆固醇(T-CHO)显著降低(P<0.01),氯离子(Cl-)降低(P<0.05);中剂量组ALP极显著升高(P<0.001),ALT显著升高(P<0.01),TG显著降低(P<0.01),BUN升高(P<0.05),T-CHO降低(P<0.05);低剂量组ALP显著升高(P<0.01);各组脏脑比值均未见统计学差异(P>0.05);各脏器病理检测与正常组比较无明显异常(P>0.05)。停药后各指标恢复正常。结论连续给药90 d7.5~15.0 g/kg(相当于临床70 kg人日用量的35~70倍)血脂宁丸可造成大鼠肝、肾功能指标升高,停药45 d后可恢复。

Objective To observe the toxicity of Xuezhining pill to normal rats, the main manifestations, involved organs and the recovery after drug withdrawal, so as to provide a toxicological basis for clinical safety administration. Methods With reference to Technical Guidelines for the Study of Chronic Toxicity of Traditional Chinese Medicine and Natural Medicine, general conditions such as weight, daily diet and daily water intake of rats were observed after 90 days of continuous administration and 45 days after drug withdrawal. 24 hours after the last administration, 10 rats were randomly selected from each group to take blood samples for routine blood test and blood biochemical test. After taking blood, the rats were killed and dissected, and the organs such as heart, liver, spleen, lung, kidney, adrenal gland, thymus, uterus, ovary, brain, stomach, small intestine, thymus, epididymis, colon and rectum were weighed. The ratio of viscera to brain was calculated except intestine, and the organs were examined by histopathology. Results During the experiment, no rats in each group died. After continuous administration for 90 days, compared with the normal group, the weight of rats in each group increased slowly(P>0.05). MCV, RET, HCT, PT and MCH in high dose group were significantly decreased(P<0.01). MCH increased significantly(P<0.01) and RET decreased significantly(P<0.01) in middle dose group. RET in low dose group decreased significantly(P<0.01). In high dose group, ALT and ALP increased significantly(P<0.001), TG decreased significantly(P<0.001), AST, BUN, Cr and ALB increased significantly(P<0.01), T-CHO decreased significantly(P<0.01) and Cl-decreased significantly(P<0.05). The ALP in low dose group increased significantly(P<0.01). There was no statistical difference between other biochemical indexes and normal group(P>0.05), and the pathological examination of each organ had no obvious abnormality. After stopping the drug, all indexes could return to normal. Conclusion After 90 days of continuous administration of 7.5~15.0 g/kg(equivalent to 35~70 times of clinical daily dosage of 70 kg), Xuezhining pill can increase the indexes of liver and renal function in rats, which can return to normal after 45 days of drug withdrawal.