纳米羟基磷灰石急性毒性试验研究  

Study on the acute toxicity of nano-hydroxyapatite

作　　者：汤京龙[1] 王硕[2] 王建宇[2] 刘丽[2] 李佳戈[2] 苑富强[2] 陆颂芳[2] 周红娇 奚廷斐[1] 

机构地区：[1]北京科技大学材料学院,北京100053 [2]中国药品生物制品检定所,北京100050 [3]云南省医疗器械检验所,昆明650034

出　　处：《北京生物医学工程》2008年第4期337-340,共4页Beijing Biomedical Engineering

基　　金：国家自然科学基金(30770579)资助

摘　　要：对纳米羟基磷灰石(nano-HAP)进行急性毒性试验研究,为长期毒性试验和其他毒理学试验提供参考依据,并初步了解nano-HAP进入血液循环系统后,是否会迁移到其它器官和组织。实验选用清洁级的110～130gWistar大鼠70只,分为7组,实验组各组剂量分别为21.66mg/kg、29.97mg/kg、41.49mg/kg、57.42mg/kg、79.48mg/kg、110.39mg/kg,以生理盐水为对照组。单次尾静脉注射,14d内观察动物的毒性症状,记录动物死亡情况。将死亡动物解剖,对动物主要脏器进行病理组织学检查。结果显示nano-HAP在Wistar大鼠身上尾静脉注射时LD50为51.79mg/kg,由病理结果推测实验动物的死亡原因是由血管栓塞所致。在一只最低剂量组死亡动物肝的汇管区及附近肝内有占位性蓝染无定型物,肝内灶性炎细胞浸润。说明nano-HAP颗粒在充分分散的情况下会通过血液循环进入到身体其它器官,因此有必要对nano-HAP的生物安全性进行进一步研究。To explore the acute toxicity of nano-hydroxyapatite （nano-HAP）, and establish a dosage regimen for subacute/subchronic and other toxicological studies as well as to provide primary information on the mode of translocation for nano-HAP in circulatory system. Acute toxicity test were carried out. 70 Wistar rats were divided into 7 groups at ran- dom,control group used saline and 6 treated groups, their dosages used were 21.66mg/kg,29.97 mg/kg,41.49 mg/kg, 57.42 mg/kg,79. 48.mg/kg, 110. 39 mg/kg respectively, which were single treated by intravenous administration. During the 14 days experiment,the body weight and toxicity symptoms of all animals were recorded. All dead animals were immediately killed by cervical dislocation and then their brain, kidney, spleen, liver, heart, lung were excised to analyse the histopathological alterations. The results showed that the fifty percent lethal doses （LDs0） of intravenous nano-HAP in rat were 51.79 mg/kg. According to histopathological analysis,thromboses may cause the death of the rats. The results of histopathological analysis also showed that some inflammatory cells were found in one rat＇s liver,which was treated under the lowest dose. These results suggested that when nano-HAP fully disperses in solution,nano-HAP particles could translocate to other organs,such as liver. Hence,it is necessary to study the biological safety of nano-HAP in details.

关 键 词：纳米 羟基磷灰石 急性毒性 

分 类 号：R318.08[医药卫生—生物医学工程]