羧甲基壳聚糖银的急性和亚急性毒性研究  

Study on acute and subacute toxicities of carboxymethyl chitosan-Ag^+

作　　者：佟巨慧[1] 迟立超[2] 张颖丽[1] 付军权[2] 林玲辉[2] 费瑞[2] 

机构地区：[1]吉林大学口腔医院牙周病科,吉林长春130021 [2]吉林大学基础医学院细胞生物学教研室,吉林长春130021

出　　处：《吉林大学学报（医学版）》2010年第4期673-677,共5页Journal of Jilin University：Medicine Edition

基　　金：吉林省科技厅科技发展计划项目资助课题(200705354);吉林省长春市科技计划项目资助课题(08QT10)

摘　　要：目的:研究羧甲基壳聚糖银(CMCT-Ag+)的急性毒性、蓄积毒性及遗传毒性,为其临床应用提供安全保障。方法:按我国《食品安全性毒理学评价程序和方法》的要求,选用SPF级ICR小鼠,随机分为空白对照组(H2O)、CMCT-Ag+组及羧甲基纤维素钠(SCMC)组或环磷酰胺(CTX)组。采用5g.kg-1剂量给小鼠灌胃1次,观察14d,检测CMCT-Ag+的半数致死量(LD50),同时观察小鼠形态并计算肝、脾、胸腺脏器系数以评价其对脏器的损害;以10g.kg-1的总给药量每天2次(间隔4h)给小鼠灌胃,观察14d,测定小鼠最大耐受性;以5g.kg-1的LD50固定剂量连续20d灌胃给药,观察和记录动物中毒表现和死亡数,测定蓄积系数,同时观察小鼠形态并计算肝、脾、胸腺脏器系数以评价其对脏器的损害;以1.25、2.50和5.00g.kg-1浓度的CMCT-Ag+连续灌胃2次(间隔24h),6h后取骨髓,检测骨髓嗜多染红细胞微核数量。结果:CMCT-Ag+的LD50>5.00g.kg-1;最大耐受量为10g.kg-1;蓄积系数大于5;CMCT-Ag+对各实验组小鼠主要脏器均无明显损害。1.25、2.50和5.00g.kg-13个剂量组的微核率分别为3.3‰、1.8‰和1.3‰,与空白对照组比较差异无显著性(P>0.05)。结论:CMCT-Ag+无毒,不能引起致突变作用,可应用于临床。Objective To studey the acute,accumulative and genetic toxicities of carboxymethyl chitosan-Ag＋（CMCT-Ag＋）in mice,and provide safety guarantee for its clinical application.Methods According to the requirements of The Procedures and Methods of Food Safety Evaluation on Toxicology,ICR mice（SPF）were randomly divided into control group（H2O）,CMCT-Ag＋ and SCMC（or CTX）groups.Gastric perfusion（GF）was applied once in ICR mice with the dosage of 5 g·kg-1.14 d later,the LD50 of CMTC-Ag＋ in mice was measured,and the organic impairments were evaluated by mice status as well as liver,spleen,and thymus indexes.For the other 14 d,GF was applied twice a day,with 4 h interval,in mice with the dosage of 10 g·kg-1.The maximum tolerance dosage of CMTC-Ag＋ was measured.Then,GF was applied once a day with the LD50 dosage of 5 g·kg-1.20 d later,the fatality of mice was counted,the accumulation coefficient was calculated,and the organic impairments were evaluated by mice status as well as liver,spleen,and thymus indexes.Finally,GF was applied once in mice for two consecutive days with the CMCT-Ag＋ concentrations of 1.25,2.50 and 5.00 g·kg-1.6 h later,the number of micronucleus in polychromatic erythrocytes（PCE）of bone marrow of mice was counted.Results The LD50 of CMCT-Ag＋ in mice was over 5 g·kg-1;the maximum tolerance dosage was 10.00 g·kg-1 and the accumulation coefficient was more than 5,hence,CMCT-Ag＋ could not impair the visceral organs of mice.The micronucleus rates in 1.25,2.50 and 5.00 g·kg-1 CMCT-Ag＋ groups were 3.3‰,1.8‰,and 1.3‰,respectively;there was no significant difference between experimental groups and control group（P〉0.05）.Conclusion CMTC-Ag＋ exhibits neither toxicity nor mutagenic reaction.It can be used in clinic.

关 键 词：羧甲基壳聚糖银 毒性 蓄积系数 微核率 

分 类 号：R965[医药卫生—药理学]