阿苯达唑壳聚糖微球抗小鼠泡球蚴药效研究

Efficacy of albendazole chitosan microsphere against echinococcus multilocularis infection in mice

目的 观察阿苯达唑（ABZ）壳聚糖微球（ABZ-CS-MPs）治疗感染多房棘球蚴小鼠的效果.方法 建立继发性感染多房棘球蚴小鼠模型,接种12周后将小鼠随机分为4组：阿苯达唑壳聚糖微球（ABZ-CS-MPs）组,阿苯达唑乳剂（ABZ-E）组,阿苯达唑片剂（ABZ-T）组,模型对照组,前3组小鼠均以75 mg/kg体质量的相应药物经口灌胃给药,模型对照组给予0.2ml生理盐水,每周3次,连续给药10周后,观察以下指标：（1）小鼠肝脏大体形态,称量囊湿重并计算抑囊率;（2）病理组织学观察;（3）高效液相色谱法（HPLC）测定小鼠血浆及肝组织匀浆中阿苯达唑亚砜（ABZ-SX）的浓度.结果 ABZ-CS-MPs治疗泡球蚴组织（E.m）明显钙化.各治疗组囊湿重分别为（0.114±0.030）、（0.247±0.086）、（0.582±0.145）g,与模型对照组的（1.273±0.198）g比较差异均有统计学意义（P＜0.05）.ABZ-CS-MPs抑制泡球蚴生长作用显著优于ABZ-E、ABZ-T组,3组抑囊率分别为：91.04％、80.60％、54.28％.苏木素-伊红（HE）染色显示：各组泡球蚴（E.m）组织有不同程度的变性,坏死,其中ABZ-CS-MPs组对E.m角质层及生发层损伤比其他治疗组严重.HPLC法结果显示：ABZ-CS-MPs组血浆及肝脏ABZ-SX浓度在各治疗组中最高,与ABZ-T组比较差异有统计学意义（P＜0.01）.结论 经口灌胃ABZ-CS-MPs对小鼠泡球蚴有明显抑制作用,壳聚糖微球促进ABZ的经肠吸收,提高其血浆、肝脏药物浓度.

Objective To observe the therapeutic efficacy of albendazole chitosan microsphere （ABZ-CS-MPs） in mice infected with echinococcus multilocularis （E.m）.Methods To establish secondary intraperitoneal infections of E.m in mice model,the 80 mice infected echinococcus multilocularis for 12 weeks were randomly divided into four groups：ABZ-CS-MPs group,albendazole oral emulsion （ABZ-E） group,albendazole tablet （ABZ-T） group and model control group,above 3 experimental groups were oral administrated with 75 mg/kg dosage; model control group were administrated with 0.2 ml saline per mouse dosage; All groups were administered with 3 times a week medication for 10 weeks.Following investigating markers were monitored after overall administration：（1） observation of morphological changes ; （2） Calculation of mean cyst weight and inhibition rate after treatment; （3） observation of Histopathological changes of the E.m vesicles ; 4） Measurement of the concentrations of albendazole sulfoxide （ABZ-SX） in plasma and liver homogenates by high-performance liquid chromatography （HPLC）.Results There were obvious collapse and calcification of E.m vesicles in ABZ-CS-MPs group,mean cyst weights of E.m tissues in each groups treated with ABZ were [（0.114 ± 0.030）,（0.247 ± 0.086）,（0.582 ± 0.145） g],there were significant differences of mean cyst weights between ABZ treated groups and model control group （P 〈 0.05）,ABZ-CS-MPs had a higher suppressive effect on vesicular development than those ABZ-E treated group and ABZ-T treated group,inhibition rate of E.m vesicles in those 3 groups were：91.04%,80.60%,54.28% respectively.Hematoxylin and eosin （HE） staining showed that there was different level of degeneration,necrosis on experimental groups,compared with other groups,germinal layer and laminate layer have severest damages in ABZ-CS-MPs treated group.Concentration of ABZ-SX in plasma and liver are much higher than ABZ-T group （P 〈0.01）.Conclusion It is concluded that ABZ-CS-MPs had higher inhibitory effect against mice infected with alveolar echinococcosis,it promoted the intestinal absorption of ABZ effectively and further increased the drug concentration in plasma and liver.