摘要
目的给大鼠连续iv和ip羟丙基-β-环糊精(HP-β-CD),观察是否产生蓄积毒性反应,确定毒性反应的靶器官及损害程度,并比较在试验剂量下2种给药方式毒性表现的差异。方法给大鼠ipHP-β-CD200mg/kg、iv54mg/kg,连给30d。观察一般状态反应,检测血液学、血液生化学、组织病理学等指标。结果除ip给予HP-β-CD200mg/kg的动物表现出不同程度的腹膜刺激症状外,动物一般状况良好,体质量、进食量、血液学及血液生化学指标均无异常。但组织病理学观察可见,2种给药方式的动物肾脏均出现皮质部分肾小管上皮明显空泡化、细胞肿胀、胞浆呈疏松淡染的圆形空泡状;肺脏均出现肺泡及间隔内有泡沫细胞。结论HP-β-CDip给药剂量为200mg/kg、iv给药剂量为54mg/kg,连给30d,表现出明显的肾脏毒性和肺脏毒性,毒性表现程度无明显差异;ip给药对腹膜有刺激性。
Objective To observe whether continuous iv and ip of hydroxypropyl-β-cyclodextion (HP-β- CD) induces cumulative toxicity and determine the target organ and severity, and to compare the toxicity in the two ways of injection. Methods Rats were daily given HP-β-CD (200 mg/kg) via ip or HP-β-CD (54 rng/kg) via tail iv for 30 d. The general conditions of rats were observed, and parameters of hematology, biochemical and histopathology were measured. Results Rats ip with HP-β-CD (200 mg/kg) showed different peritoneal irritations. Other rats were in good condition, without abnormal parameters in body weight, food intake, hematology and blood biochemistry. However, histopathologic investigation showed that ip and iv of HP-β-CD caused changes in kidney: the marked vacuolization of the renal tubular epithelial in the renal cortex, cell swelling, round vacuolar of the cytoplasm. They also caused changes in lungs: foam cells in the alveolar and the alveolar septum. Conclusion Consecutive ip of HP-β-CD (200 mg/kg) and iv of HP-β-CD (54 mg/kg) for 30 d show obvious nephrotoxicity and pulmonary toxicity. No significant differences appear in the toxicity caused by the two ways of injection ip of HP-β-CD (200 mg/kg) can cause peritoneal irritation in rats.
出处
《现代药物与临床》
CAS
2009年第6期361-364,共4页
Drugs & Clinic
基金
国家科技支撑计划地方重大专项(2007BAQ00162)
关键词
羟丙基-Β-环糊精
静脉注射
腹腔注射
毒性
Hydroxypropyl-β-cyclodextion
intravenous injection
intraperitoneal injection
toxicity