首页|三氧化二砷联合阿苯达唑对细粒棘球蚴生长的影响

三氧化二砷联合阿苯达唑对细粒棘球蚴生长的影响

扫码查看
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 6 μmol/L)联合ABZ在体外条件下作用于原头节,分组如下:3 μmol/L ATO、6 μmol/L ATO、100 μmol/L ABZ、3 μmol/L ATO+100 μmol/L ABZ和6 μmol/L ATO+100 μmol/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 2d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 6 μmol/L ATO+100 μmol/L ABZ组原头节的抑制作用最强,3 μmol/L ATO+100 μmol/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,6 μmol/L ATO+100 μmol/L ABZ作用 3d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.
Effect of arsenic trioxide combined with albendazole on the growth of Echinococcus granulosus
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 under an 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 stronger effect 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 layer of the Protoscolex showed insect-like changes,apex mutation,head hook defect and microhair loss.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.

arsenic trioxideprotoscolecesalbendazolecombined effect

邢国强、张慧、吕海龙

展开 >

250031 济南市,山东省立第三医院

四川省成都市第三人民医院

三氧化二砷 原头节 阿苯达唑 联合作用

国家自然科学基金项目

U1303121

2024

河北医药
河北省医学情报研究所

河北医药

CSTPCD
影响因子:1.075
ISSN:1002-7386
年,卷(期):2024.46(4)
  • 20