纳米HNS、TATB及LLM-105的RAW264.7巨噬细胞毒性及其机制  

Cytotoxicity and Mechanisms of Nanoscale HNS,TATB and LLM-105 to RAW264.7 Macrophage

作　　者：唐灿 黄兵[1] 刘柳[1] 范美坤 周阳[1] TANG Can;HUANG Bing;LIU Liu;FAN Mei-kun;ZHOU Yang(Institute of Chemical Materials,CAEP,Mianyang 621999,China;School of Earth and Environmental Engineering,Southwest Jiaotong University,Chengdu 611756,China)

机构地区：[1]中国工程物理研究院化工材料研究所,四川绵阳621999 [2]西南交通大学地球科学与环境工程学院,四川成都611756

出　　处：《含能材料》2020年第8期792-797,共6页Chinese Journal of Energetic Materials

基　　金：国民核生化灾害防护国家重点实验室基金资助(SKLNBC2018-18)。

摘　　要：纳米炸药具有独特的性能优势而受到了广泛关注,但是对该类材料毒性认识的缺乏会限制其工业化应用。探讨了三种典型纳米级炸药,即六硝基茋(HNS)、三氨基三硝基苯(TATB)和2,6-二氨基-3,5-二硝基吡嗪-1-氧化物(LLM-105)的细胞毒性及其可能机制。以小鼠巨噬细胞RAW264.7细胞为受试物进行染毒实验,采用CCK-8比色法检测细胞活性,同时对乳酸脱氢酶(LDH)、过氧化物歧化酶(SOD)活性、丙二醛(MDA)的含量进行分析以判断细胞死亡机制。结果表明,三种纳米级炸药都可以导致RAW264.7细胞活性显著下降,并呈现剂量相关性;其对RAW264.7细胞的半抑制浓度(IC50)分别为49.3,211.3,6.6μg·mL^-1。随染毒剂量升高,细胞出现皱缩、触角增多或伸长、圆化等不规则形态变化;上清液中LDH的活性也呈上升趋势。另外还发现TATB与LLM-105染毒组细胞内SOD活力降低,LLM-105染毒组细胞内MDA含量升高。结果表明,纳米级HNS、TATB、LLM-105对RAW264.7细胞具有显著毒性作用;而破坏细胞膜完整性、引发氧化应激,是细胞死亡的重要原因。Nano explosives have attracted wide attention due to their unique performance advantage,but the lack of understanding of this type of biological toxicity will limit their industrial application. In order to determine the toxicity effect of nanometer hexanitrophosphonium(HNS),triaminotrinitrobenzene(TATB),and 2,6-diamino-3,5-dinitropyrazine-1-oxide(LLM-105)on RAW264.7 macrophages. The RAW 264.7 cells were treated with different concentrations of nanoparticles for 24 h. CCK-8 assays were applied for testing macrophage cytotoxicity in vitro,which were based on mitochondrial activity evaluation. In order to determine the mechanism of cell death,lactate dehydrogenase(LDH) in supernatant,superoxide dismutase(SOD) and malondialdehyde(MDA)intra-cellular fluid were determined. The morphologic change of RAW 264.7 was also observed. The results showed that all three types of nano-explosives could significantly reduce the activity of RAW264.7 cells and showed a dose-dependent relationship. Their half inhibitory concentrations(IC50)on RAW264.7 cells were 49.3,211.3 μg·mL^-1,and 6.6 μg·mL^-1,respectively. The RAW264.7 cells exhibited various morphological changes such as shrinkage and roundness. The LDH activity in the supernatant also showed an upward trend. In addition,TATB and LLM-105 decreased the activity of SOD,the content of MDA increased with concentration of LLM-105. The results clearly indicated that nano-matter HNS,TATB,and LLM-105 have toxic effects on RAW264.7 cells,destroying the integrity of the cell membrane and triggering oxidative stress are important elements of cytotoxicity.

关 键 词：六硝基茋(HNS) 三氨基三硝基苯(TATB) 2 6-二氨基-3 5-二硝基吡嗪-1-氧化物(LLM-105) RAW264.7细胞 细胞毒性 

分 类 号：TJ55[兵器科学与技术—军事化学与烟火技术] R994.7[医药卫生—毒理学]