水溶性印迹壳聚糖对贫铀致细胞毒性的解毒作用  

Detoxication effect of water-soluble imprinted cross-linked chitosan on depleted uranium induced toxicity to renal cells

作　　者：张晓菲[1,2] 李超[3] 赵长琦[1] 刘丽宏[2] 

机构地区：[1]北京师范大学生命科学学院,北京100875 [2]中国人民解放军第二炮兵总医院药剂科,北京100088 [3]中国医药集团总公司四川抗菌素工业研究所,四川成都610052

出　　处：《药学学报》2011年第5期513-520,共8页Acta Pharmaceutica Sinica

基　　金：全军"十一五"科技攻关课题(2006203003)

摘　　要：利用印迹技术提高壳聚糖螯合铀的性能,探讨水溶性印迹壳聚糖是否能对贫铀(depleted uranium,DU)染毒细胞有解毒作用。首先筛选对铀酰离子(UO22+)螯合率高的印迹壳聚糖,再以人肾近端小管上皮细胞株(HK-2)DU(500μmol·L-1)染毒为模型,实验组加入壳聚糖(400 mg·L-1)和阳性对照组加入二乙烯三胺五乙酸(DTPA,50 mg·L-1)与DU共同作用下培养细胞。3个Cu2+印迹壳聚糖对DU螯合量超过49μg.mg-1,明显高于相应的非印迹壳聚糖;MTT测定DU污染组的细胞存活率为57.3%,加入Cu2+印迹戊二醛交联羧甲基壳聚糖Cu-P-CMC的实验组和DTPA螯合剂保护组的细胞存活率升高至88.7%和72.6%,细胞内DU蓄积量明显减少,细胞膜损伤和DNA损伤减轻,并且Cu-P-CMC解毒效果优于DTPA;透射电镜超微观察到,加入壳聚糖后的DU被壳聚糖螯合形成多个绒球,聚簇成串状或大团簇状,这种螯合物难进入细胞内而使细胞内DU蓄积量大大减少,因此缓解了DU对细胞的毒性。To investigate whether a series of water-soluble cross-linked chitosan derivates synthesized in the guide of imprinting technology could be used as a uranium chelating agent to protect ceils exposed to depleted uranium （DU）, the imprinted chitosan derivates with high UO2^2＋ chelating ability were screened, and cell model of human renal proximal tubule epithelium cells （HK-2） exposed to DU （500 μmol·L^-l） was built, chitosan derivates （400 mg·L^-1） was added to test group and diethylenetriaminepentaacetic acid （DTPA, 50 mg.L^-1） was added to positive control group. The results showed that three Cu^2＋ imprinted chitosan derivates had higher uranium chelating ability （〉49 μg·mg^-1） than chitosan and non-imprinted chitosan derivates. Compared to the cells exposed to DU only, survival of cells in group added chitosan derivates rose up significantly （increased from 57.3% to 88.7%, and DTPA to 72.6%）, and DU intracellular accumulation decreased, membrane damage and DNA damage also eased. Among the imprinted chitosan derivates, Cu^2＋ imprinted penta dialdehyde cross-linked carboxymethyl chitosan （Cu-P-CMC） was the best, and better than DTPA. From ultrastructure observation, the DU precipitates of test group added Cu-P-CMC were most grouped in a big hairy clusters in a string together outside cells. It is possible that the DU-chitosan derivates precipitates are too big to enter intocells, and from this way, the DU uptake by cells decreased so as to detoxication.

关 键 词：贫铀 铀螯合剂 印迹壳聚糖 解毒 人肾近端小管上皮细胞 

分 类 号：R818.03[医药卫生—放射医学]