中国药理学与毒理学杂志Issue(2)：255-261,7.DOI:10.3867/j.issn.1000-3002.2014.02.019
纳米化酰胺磷定对梭曼中毒小鼠乙酰胆碱酯酶的重活化作用
Reactivation of nanoparticulated HI-6 on acetylcholinesterase activity in soman poisoned mice
摘要
Abstract
OBJECTIVE Based on different drug loading models,three types of nanoparticulated HI-6 were prepared and their reactivations on inhibited acetylcholinesterase (AChE)in peripheral and central nervous syste ms were evaluated and compared in so man-intoxicated mice.METHODS Three kinds of nano-reactivators including HI-6 loaded human serum albunin nanoparticle (HSA-HI-6 NP),HI-6 absorptive mesoporous silica nanoparticle(MSN-HI-6),polylactico-glycolic acid nanoparticle coated HI-6 (PLGA-HI-6 NP)were prepared.The characteristic of all blank nanocarriers was observed through elec-tron microscope.HI-6 release rate of nano-reactivators was also determined in vitro.Then the reactiva-tion rate of nano-reactivators at a constant HI-6 dosage(22 mg·kg -1 )on so man-inhabited AChE both in blood and brain was assessed the so man intoxicated mice(120 μg·kg -1 ,sc).RESULTS All the syn-thetic nanocarriers met the de mand for nanodrug use in vivo.The rate of HI-6 release of nano-reactiva-tors was HI-6 >HSA-HI-6 NPs >MSN-HI-6 >PLGA-HI-6 NP in vitro.On the reactivations of so man-inhibited mice blood AChE,the free HI-6 and HSA-HI-6 NPs,as well as MSN-HI-6 showed co mparable reactivation rates(20% -30%)but were greater than that of PLGA-HI-6 NPs (6.2%)(P <0.01 ). However on the reactivations of so man-inhibited mice brain AChE,the reactivation rate of HSA-HI-6 NP (15.3%)was significantly higher than that of PLGA-HI-6 NP(3.3%)and free HI-6(6.3)(P<0.01 ).In addition,MSN-HI-6 group had a significant reactivation rate compared to PLGA-HI-6 NPs(P <0.01 ). But there was no statistic difference between MSN-HI-6 and free HI-6.CONCLUSION The reactivation potency changed obviously with different drug loading models and HSA-HI-6 NPs had the most potent reactivation on so man-inhibited AChE in both blood and brain.关键词
神经性毒剂/乙酰胆碱酯酶/纳米化HI-6/重活化作用Key words
nerve agents/acetylcholinesterase/nano-reactivator/HI-6/reactivation分类
医药卫生引用本文复制引用
王飞剑,王永安,房彤宇,杨军,程凤,李万华,聂志勇,骆媛,隋昕,魏朝,郑志兵..纳米化酰胺磷定对梭曼中毒小鼠乙酰胆碱酯酶的重活化作用[J].中国药理学与毒理学杂志,2014,(2):255-261,7.基金项目
国家新药创制重大专项（2011 ZXJ09102-05C）；国家新药创制重大专项（2011 ZXJ09305）；全军医学科技“十二五”重大项目（AWS11 C004）；全军医学科技“十二五”重点项目（BWS12J042）；总后青年培育基金（13QNPQ152）@@@@ The project supported by National Major Special Project of Drug Develop ment of China （2011 ZX09102-05C）；National Major Special Project of Drug Develop ment of China（2011 ZXJ09305）；The Twelfth Five Year Major Special Project of Medicine Research of PLA（AWS11 C004）；and The Twlfth were Year Mega-Special Project of PLA（BWS12J042）；The Youth Cultivation Foundation of the General Logistics Depart ment of PLA （）
