清肝化瘀颗粒对不同性别大鼠的长期毒性研究  

Study on the long-term toxicity of Qinggan Huayu granule in rats of different genders

作　　者：朱晓燃 索菲娅 杨振寰[1] 姚树坤[2] ZHU Xiaoran;SUO Feiya;YANG Zhenhuan;YAO Shukun(Beijing University of Traditional Chinese Medicine,Beijing 100029,China;China-Japanese Friendship Hospital,Beijing 100029,China)

机构地区：[1]北京中医药大学,北京100029 [2]中日友好医院,北京100029

出　　处：《现代中西医结合杂志》2022年第3期303-313,333,共12页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：北京市科委G20工程创新研究十病十药研发项目(Z171100001717008)。

摘　　要：目的观察清肝化瘀颗粒连续灌胃对不同性别大鼠的长期毒性,为拟定临床人体用药安全剂量提供参考。方法将160只SD大鼠随机分成4组,每组40只,雌雄各半。清肝化瘀颗粒低、中、高剂量组分别予1.95 g/kg、3.90 g/kg、7.80 g/kg的清肝化瘀颗粒灌胃,对照组给予等体积实验动物饮用水灌胃,均1次/d,连续灌胃6个月。分别在给药中期(第91天)、给药末期(雄鼠第182天、雌鼠第183天)及恢复期(灌胃结束后第28天)观察各组大鼠的一般状况、体重、摄食量、尿量及饮水量变化,检测血液常规、血清生化学指标及脏器系数、组织病理学变化。结果各组大鼠实验期间均未见死亡及异常生命活动表现,摄食量、尿量及饮水量均正常,仅清肝化瘀颗粒高剂量组大鼠体重在给药7 d明显低于对照组(P<0.05)。给药第91天及给药末期,清肝化瘀颗粒各剂量组不同性别大鼠尿酮体、尿蛋白量、尿白细胞计数及血液红细胞计数、血细胞比容(HCT)、平均红细胞容积(MCV)、血红蛋白(Hb)、血糖(GLU)、总胆固醇(TC)、γ-谷氨酰转肽酶(GGT)、总胆红素(TBil)及钠离子(Na^(+))、钾离子(K^(+))、氯离子(Cl^(-))水平出现变化,但无明确的毒理学意义,灌胃结束后第28天尿液指标、血液常规各项指标均正常。清肝化瘀颗粒中、高剂量组与对照组比较部分脏器系数显著增高,清肝化瘀颗粒高剂量组可出现与受试药物相关的病变程度较轻的病理改变;灌胃结束后第28天除清肝化瘀颗粒高剂量组雄性大鼠的甲状腺轻度病变外,其余脏器未见明显的毒性损伤。结论清肝化瘀颗粒对大鼠的长期毒性较低,17.44 g生药/kg(相当于临床拟用剂量的26倍)为大鼠的无明显不良影响剂量。Objective It is to observe the long-term toxicity of Qinggan Huayu granule after continuous intragastric administration in rats of different genders, and provide reference for clinical human medication. Methods 160 SD rats were randomly divided into 4 groups, 40 rats in each group, half male and half male. Qinggan Huayu granules low-dose, middle-dose and high-dose groups were respectively given 1.95 g/kg, 3.90 g/kg, 7.80 g/kg Qinggan Huayu granules by gavage, and the control group was given equal volume of experimental animals drinking water by gavage, all 1 time/d, continuous treated for 6 months. The general condition, body weight, food intake, urine volume and water intake of the rats in each group were observed, and blood routine, serum biochemical indexes, organ coefficients were detected, and histopathological changes were observed in the mid-administration period(the 91 st day), the end of the administration period(the 182 nd day of the male rat, the 183 rd day of the female rat) and the recovery period(the 28 th day after the end of the gavage). Results During the experiment, no death or abnormal life activities were found in the rats in each group, and the food intake, urine output and water intake in the rats were normal. Only the weight of the rats in the high-dose Qinggan Huayu granules group was significantly lower than that in the control group at 7 d after administration(P<0.05). On the 91 st day of administration and at the end of administration, the levels of urine ketone bodies, urine protein content, urine white blood cell count, blood red blood cell count, hematocrit(HCT), mean corpuscular volume(MCV), hemoglobin(Hb), blood glucose(GLU), total cholesterol(TC), γ-glutamyltransferase(GGT), total bilirubin(TBil) and sodium ion(Na^(+)), potassium ion(K^(+)), chloride ions(Cl^(-)) changed, but there was no clear toxicological significance. The urine indexes and blood routine indexes were normal on the 28 th day after the end of the gavage. Compared with the control group, the coefficients of some

关 键 词：长期毒性 大鼠 毒理学 肝癌 清肝化瘀颗粒 

分 类 号：R-332[医药卫生]