三氧化二砷联合阿苯达唑对细粒棘球蚴生长的影响  

Effect of arsenic trioxide combined with albendazole on the growth of Echinococcus granulosus

作　　者：邢国强 张慧 吕海龙 XING Guoqiang;ZHANG Hui;LV Hailong(Shandong Provincial Third Hospital,Shandong,Jinan 250031,China;不详)

机构地区：[1]山东省立第三医院,济南市250031 [2]四川省成都市第三人民医院

出　　处：《河北医药》2024年第4期516-519,524,共5页Hebei Medical Journal

基　　金：国家自然科学基金项目(编号:U1303121)。

摘　　要：目的研究体外条件下三氧化二砷(ATO)联合阿苯达唑(ABZ)对细粒棘球蚴原头节生长作用的影响,初步探讨联合用药治疗肝包虫病的可行性。方法采用不同浓度的ATO(3和6μmol/L)联合ABZ在体外条件下作用于原头节,分组如下:3μmol/L ATO、6μmol/L ATO、100μmol/L ABZ、3μmol/L ATO+100μmol/L ABZ和6μmol/L ATO+100μmol/L ABZ。光镜下通过0.1%伊红染色法观察原头节的活力及形态变化;扫描电子显微镜下观察原头节的超微结构变化;各组药物作用2 d后,借助半胱氨酸天冬氨酸蛋白酶-3(caspase-3)活性检测试剂盒测定caspase-3酶活力。采用ELISA法检测原头节内抗氧化酶(SOD、HO-1)活性水平。结果6μmol/L ATO+100μmol/L ABZ组原头节的抑制作用最强,3μmol/L ATO+100μmol/L ABZ组次之。联合作用组对原头节超微结构的损伤明显大于ABZ单独作用组,6μmol/L ATO+100μmol/L ABZ作用3 d后原头节表层出现虫蚀样改变、顶突变形、头钩缺损及微毛脱落。原头节在培养4d后,联合作用组原头节caspase-3活力[(43.34±1.07)μmol/L]显著高于ABZ单药作用组[(32.58±0.73)μmol/L](F=859.754,P<0.05),且具有剂量依赖性。ATO作用后原头节内SOD、HO-1活性显著下降(P<0.05),呈现时间及剂量依赖性。结论ATO与ABZ联合可显著抑制细粒棘球蚴原头节生长,且抑制作用强于单独用药,其协同作用机制可能与改变原头节内氧化应激系统有关,然而其具体机制尚需进一步研究。Objective To explore the effect of arsenic trioxide(ATO)combined with albendazole(ABZ)on the growth of Protoscolex of Echinococcus granulosus,and to explore the feasibility of ATO combined with ABZ in the treatment of hepatic echinococcosis.Methods Protoscolex of Echinococcus granulosus was in vitro cultured with 3μmol/L ATO,6μmol/L ATO,100μmol/L ABZ,3μmol/L ATO+100μmol/L ABZ and 6μmol/L ATO+100μmol/L ABZ,respectively.Viability and morphological structure were detected with 0.1%eosin staining undeRan inverted light microscope.The ultrastructural alterations were visualized by scanning electron microscopy(SEM).Meanwhile,caspase-3 activity assay kits were performed.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of SOD and HO-1.Results Treatment of 6μmol/L ATO+100μmol/L ABZ exerted the strongest inhibitory effect on the growth of Protoscolex of Echinococcus granulosus,followed by the combined treatment of 3μmol/L ATO+100μmol/L ABZ.The combined treatment of ATO and ABZ produced a strongeReffect on the ultrastructural damage than that of a single treatment of ABZ.After 3-day treatment of 6μmol/L ATO+100μmol/L ABZ,the surface layeRof the Protoscolex showed insect-like changes,apex mutation,head hook defect and microhaiRloss.After treatment for 4 days,the caspase-3 activity was significantly higher in Protoscolex treated with ATO combined with ABZ than that treated with ABZ alone([43.34±1.07]μmol/L vs[32.58±0.73]μmol/L,F=859.754,P<0.05),showing a dose-dependent manner.The activities of SOD and HO-1 were significantly lower after ATO treatment,showing a time-and dose-dependent manneR(P<0.05).Conclusion The combination of ATO and ABZ can significantly inhibits the growth of Protoscolex of Echinococcus granulosus compared to a single drug.The exact mechanism still needs a further exploration.

关 键 词：三氧化二砷 原头节 阿苯达唑 联合作用 

分 类 号：R53[医药卫生—内科学]