蓖麻毒素细胞毒性及其中毒小鼠组织病理改变  

Cytotoxicity of ricin and pathological changes in tissues of ricin-intoxicated mice

作　　者：董娜[1,2] 武军华[1] 贾培媛[1] 李倩[1] 温新宇[2] 冯泽国[2] 周建平[1] 王玉霞[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]解放军总医院,北京100853

出　　处：《解放军医学院学报》2013年第10期1048-1051,共4页Academic Journal of Chinese PLA Medical School

基　　金：国家"973"重点基础研究发展规划项目(2010CB933904);国家"十二五"科技支撑资助项目(2011BAD26B02)~~

摘　　要：目的探讨蓖麻毒素对不同细胞的细胞毒性及小鼠各主要组织脏器毒性的基本病理改变。方法应用MTT法检测不同浓度(1 ng/ml,10 ng/ml,100 ng/ml,1μg/ml)蓖麻毒素给药24 h对不同细胞株(Caco-2,MDCK,MDCK-MDR1,HepG2,H1299)的细胞活性的影响;经灌胃方式使小鼠中毒,中毒24 h观察蓖麻毒素对小鼠脏器的基本病理变化,测定相关生化指标,分析蓖麻毒素对小鼠肝肾损伤。结果不同浓度的蓖麻毒素对Caco-2,MDCK,MDCK-MDR1,HepG2和H1299细胞均有一定的毒性,随着毒素浓度的升高,细胞毒性亦呈上升趋势,有明显量效关系,其中MDCK细胞对蓖麻毒素最为敏感。病理学检测显示蓖麻毒素可致小鼠肾小球出血及部分肾血管内皮细胞缺如,肝细胞水肿、近端肠绒毛损伤、轻度坏死性肺炎并有炎性细胞浸润。血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、总胆红素(TBIL)、甘油三酯(TG)、肌酐(CREA)均升高,表明小鼠中毒3 h内肝功能和肾功能已出现一定程度的损伤。结论蓖麻毒素通过抑制蛋白质合成而导致细胞坏死。不同细胞对蓖麻毒素具有不同的敏感性,表现为蓖麻毒素中毒早期,动物即可出现严重的肝、肾损伤。Objective To study the cytotoxicity of ricin to different cells and the pathological changes in major organizations of ricin-intoxicated mice. Methods Twenty-four hours after the mice administered ricin at different concentrations （1 ng/ml, 10 ng/ml, 100 ng/ml, 1μg/ml）, its effect on the viability of different cell lines （Caco-2, MDCK, MDCK-MDR1, HepG2, H1299） was assayed by MTT assay, pathological changes in their major organizations were observed, related biochemical indicators were detected, and ricin-induced damage to the liver and kidney of mice was analyzed. Results Different concentrations of ricin showed its toxicity to Caco-2, MDCK, MDCK-MDR1, HepG2, and H1299 cells in a dose-dependent manner, namely its cytotoxicity increased with its concentration. The MDCK cells were most sensitive to ricin. Pathological examination showed that ricin could lead to glomerular bleeding, renovascular endothelial deficit, edema of liver cells, proximal intestinal villus injury, and mild necrotizing pneumonia with inflammatory cell infiltration. The serum levels of ALT, AST, ALP, TBIL, TG and CREA were elevated in the mice, indicating that the liver and renal function of mice were damaged 3 h after they were intoxicated by ricin. Conclusion Ricin can induce the necrosis of cells by inhibiting the synthesis of protein and is manifested as severe liver and kidney injury during its early intoxication. The sensitivity of different cell lines to ricin is different.

关 键 词：蓖麻毒素 细胞毒性 病理改变 

分 类 号：R963[医药卫生—微生物与生化药学]