中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2014年
2期
255-261
,共7页
王飞剑%杨军%程凤%李万华%聂志勇%骆媛%隋昕%魏朝%郑志兵%王永安%房彤宇
王飛劍%楊軍%程鳳%李萬華%聶誌勇%駱媛%隋昕%魏朝%鄭誌兵%王永安%房彤宇
왕비검%양군%정봉%리만화%섭지용%락원%수흔%위조%정지병%왕영안%방동우
神经性毒剂%乙酰胆碱酯酶%纳米化HI-6%重活化作用
神經性毒劑%乙酰膽堿酯酶%納米化HI-6%重活化作用
신경성독제%을선담감지매%납미화HI-6%중활화작용
nerve agents%acetylcholinesterase%nano-reactivator%HI-6%reactivation
目的：评价比较基于不同载药模式的纳米化酰胺磷定（HI-6）对梭曼中毒小鼠外周及中枢乙酰胆碱酯酶（AChE）的重活化作用。方法制备以人血清白蛋白纳米粒（HSA NP）为载体挂载 HI-6（HSA-HI-6 NP）、聚乳酸-羟基乙酸纳米粒（PLGA NP）为载体包裹 HI-6（PLGA-HI-6 NP）及纳米多孔硅球（MSN）为载体吸附 HI-6（MSN-HI-6）的3种纳米化 HI-6。电镜进行物理表征；测定体外释药速率。观察梭曼染毒（120μg·kg -1，sc）小鼠 iv 给予含恒量 HI-622 mg·kg -1的3种纳米化 HI-6对外周及中枢中毒 AChE 的重活化作用。结果3种纳米载体均符合纳米药物基本特征。体外释药速率为 HI-6＞HSA-HI-6 NP ＞MSN-HI-6＞PLGA-HI-6 NP。对中毒小鼠全血 AChE 的重活化作用结果显示给予 HSA-HI-6 NP，MSN-HI-6及HI-6组中毒小鼠全血 AChE 的重活化率在20％～30％，组间比较无显著差异；但均显著高于 PLGA-HI-6 NP（6．2％）给药组（P ＜0．01）；在中毒小鼠脑 AChE 的重活化作用结果中，HSA-HI-6 NP 组重活化率（15．3％）显著高于 PLGA-HI-6 NP（3．3％）组及 HI-6组（6．3％）（P＜0．01）；MSN-HI-6组（10．2％）则仅显著高于 PLGA-HI-6 NP（3．3％）给药组（P ＜0．01）。结论不同载药模式的纳米化 HI-6对外周及中枢中毒AChE 的重活化效率存在显著差异，HSA-HI-6 NP 对外周及中枢中毒 AChE 均具较高重活化作用。
目的：評價比較基于不同載藥模式的納米化酰胺燐定（HI-6）對梭曼中毒小鼠外週及中樞乙酰膽堿酯酶（AChE）的重活化作用。方法製備以人血清白蛋白納米粒（HSA NP）為載體掛載 HI-6（HSA-HI-6 NP）、聚乳痠-羥基乙痠納米粒（PLGA NP）為載體包裹 HI-6（PLGA-HI-6 NP）及納米多孔硅毬（MSN）為載體吸附 HI-6（MSN-HI-6）的3種納米化 HI-6。電鏡進行物理錶徵；測定體外釋藥速率。觀察梭曼染毒（120μg·kg -1，sc）小鼠 iv 給予含恆量 HI-622 mg·kg -1的3種納米化 HI-6對外週及中樞中毒 AChE 的重活化作用。結果3種納米載體均符閤納米藥物基本特徵。體外釋藥速率為 HI-6＞HSA-HI-6 NP ＞MSN-HI-6＞PLGA-HI-6 NP。對中毒小鼠全血 AChE 的重活化作用結果顯示給予 HSA-HI-6 NP，MSN-HI-6及HI-6組中毒小鼠全血 AChE 的重活化率在20％～30％，組間比較無顯著差異；但均顯著高于 PLGA-HI-6 NP（6．2％）給藥組（P ＜0．01）；在中毒小鼠腦 AChE 的重活化作用結果中，HSA-HI-6 NP 組重活化率（15．3％）顯著高于 PLGA-HI-6 NP（3．3％）組及 HI-6組（6．3％）（P＜0．01）；MSN-HI-6組（10．2％）則僅顯著高于 PLGA-HI-6 NP（3．3％）給藥組（P ＜0．01）。結論不同載藥模式的納米化 HI-6對外週及中樞中毒AChE 的重活化效率存在顯著差異，HSA-HI-6 NP 對外週及中樞中毒 AChE 均具較高重活化作用。
목적：평개비교기우불동재약모식적납미화선알린정（HI-6）대사만중독소서외주급중추을선담감지매（AChE）적중활화작용。방법제비이인혈청백단백납미립（HSA NP）위재체괘재 HI-6（HSA-HI-6 NP）、취유산-간기을산납미립（PLGA NP）위재체포과 HI-6（PLGA-HI-6 NP）급납미다공규구（MSN）위재체흡부 HI-6（MSN-HI-6）적3충납미화 HI-6。전경진행물리표정；측정체외석약속솔。관찰사만염독（120μg·kg -1，sc）소서 iv 급여함항량 HI-622 mg·kg -1적3충납미화 HI-6대외주급중추중독 AChE 적중활화작용。결과3충납미재체균부합납미약물기본특정。체외석약속솔위 HI-6＞HSA-HI-6 NP ＞MSN-HI-6＞PLGA-HI-6 NP。대중독소서전혈 AChE 적중활화작용결과현시급여 HSA-HI-6 NP，MSN-HI-6급HI-6조중독소서전혈 AChE 적중활화솔재20％～30％，조간비교무현저차이；단균현저고우 PLGA-HI-6 NP（6．2％）급약조（P ＜0．01）；재중독소서뇌 AChE 적중활화작용결과중，HSA-HI-6 NP 조중활화솔（15．3％）현저고우 PLGA-HI-6 NP（3．3％）조급 HI-6조（6．3％）（P＜0．01）；MSN-HI-6조（10．2％）칙부현저고우 PLGA-HI-6 NP（3．3％）급약조（P ＜0．01）。결론불동재약모식적납미화 HI-6대외주급중추중독AChE 적중활화효솔존재현저차이，HSA-HI-6 NP 대외주급중추중독 AChE 균구교고중활화작용。
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.
