机构地区:[1]广州中医药大学中药资源科学与工程研究中心,广州510006 [2]广州中医药大学中药学院,广州510006 [3]广州中医药大学,广州510006
出 处:《中国实验方剂学杂志》2017年第12期151-156,共6页Chinese Journal of Experimental Traditional Medical Formulae
基 金:广东省科技计划项目(2016ZC0098);广东省教育部科技部产学研结合项目(2012B091100183)
摘 要:目的:观察茜草70%乙醇提取物长期给药对大鼠肝、肾及结肠毒性的影响,为临床合理用药提供一定的依据。方法:在SPF级实验条件下,将48只Wistar大鼠随机分为空白组和茜草高、中、低剂量(30,10,5 g·kg^(-1),分别相当于临床人拟定剂量的36,12,6倍)组,每组12只,雌雄各半。空白组给予等体积蒸馏水,连续灌胃给药60 d。给药期间,观察记录大鼠的一般情况(行为活动,精神状态,饮食量,毛色光泽,大小便颜色);停止给药后,观察动物的血液生化指标、脏器系数及病理组织学变化等。结果:与空白组比较,茜草各剂量组大鼠肝,肾及脾脏器指数明显增大(P<0.05);丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)的水平显著升高(P<0.01);雄性大鼠β2-微球蛋白(β2-MG)和胱抑素C(Cys-C)明显升高(P<0.05,P<0.01),雌性大鼠仅茜草高剂量组β2-MG显著升高(P<0.01),胱抑素C(Cys-C)与空白组比较无统计学差异。茜草各剂量组尿素氮(BUN)与空白组比较无统计学差异,茜草各组肝、肾组织形态与空白组比较没有明显的病理改变。茜草各剂量组雌雄大鼠的结肠组织形态、结肠黑色素染色和结肠上皮细胞凋亡率与空白组比较均无明显变化。结论:茜草70%乙醇提取物长期给药剂量≥5 g·kg^(-1),具有轻微的肝、肾毒性;对结肠无毒性作用,不能导致大鼠结肠黑变病的发生。Objective: To study the effect of Rubiae Radix et Rhizoma 70% ethanol extract on hepatotoxicity, nephrotoxicity and colonic toxicity in rats after long term use, and provide a certain basis for clinical rational drug use. Method: The 48 Wistar rats were randomly divided into blank control group, Rubiae Radix et Rhizoma high dose, medium dose and low dose groups (30, 10, 5 g·kg^-1, respectively equivalent to 36, 12, 6 times of clinical human dose) under SPF experimental conditions, n = 12 in each group, 6 males and 6 females. The rats in control group received the same volume of distilled water, and all these rat were continuously lavaged for 60 days. During the treatment, the general situations of rats (activities, mental state, diet, color luster, urine color) were observed and recorded. After the last oral administration, the blood biochemical indicators of animals, viscera coefficient and the change of pathological histology were observed. Result: As compared with the blank group, liver, kidney and spleen indexes were increased in each dose Rubiae Radix et Rhizoma groups ( P 〈 0.05 ) ; the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased significantly (P 〈0.01 ) ; the levels offl2-MG and Cys-C in male rats were also increased (P 〈0.05, P 〈0.01 ) , but in female rats, fl2-MG was significantly increased only in high dose group (P 〈 0.01 ) , and there was no difference in Cys-C as compared with blank group. In addition, there was no statistical difference in urea nitrogen (BUN) between each dose Rubiae Radix et Rhizoma groups and blank group, and there were no obvious pathological changes in liver and kidney morphology. Finally, colon tissue morphology, melanin staining and cell apoptosis in each dose group of Rubiae Radix et Rhizoma had no significant differences as compared with the blank control group. Conclusion: Rubiae Radix et Rhizoma 70% ethanol extract had mild hepatotoxicity and nephrotoxicity, but had no t
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