不同药物对小鼠肝细粒棘球蚴术后感染的抑制作用

Inhibitory effects of different drugs on the post-operative infection of hepatic echinococcus granulosus in mice

目的:探讨不同药物对小鼠肝细粒棘球蚴感染的抑制作用,了解增强宿主免疫功能对小鼠肝细粒棘球蚴感染的影响.方法:取包虫囊液成功免疫小鼠,分为药物治疗组和模型对照组.肝脏接种原头蚴前1wk及接种后1mo,药物治疗组分别用阿苯哒唑脂质体、槐耳浸膏及阿苯哒唑脂质体联合槐耳浸膏治疗,接种头节时各药物治疗组再分为4组,每组头节分别使用750mL/L乙醇、200g/L高渗盐水、阿苯哒唑脂质体及平衡液处理后接种,模型对照组头节用平衡液处理后直接接种,接种后3mo观察小鼠肝细粒棘球蚴大体和病理变化,检测小鼠脾脏指数、外周血IgG和IgE水平,并用流式细胞仪检测小鼠外周血CD4+和CD8+淋巴细胞的百分率.结果:联合治疗组中小鼠肝细粒棘球蚴生发层和角质层破坏较严重.各药物治疗组小鼠脾脏指数、IgE水平明显低于模型对照组(3.84±0.86,3.95±1.01,3.27±0.52vs5.46±0.52;0.06±0.08μg/L,0.07±0.08μg/L,0.03±0.03μg/Lvs0.20±0.02μg/L,均P<0.01),其中联合药物治疗组降低最为明显;药物治疗组IgG水平与模型对照组相比无显著性差异.药物治疗组CD8+水平明显低于模型对照组(16.60±3.89,18.18±3.90,15.38±2.63vs32.90±4.71,均P<0.01),CD4+/CD8+明显高于模型对照组(3.21±0.70,3.05±0.66,3.53±0.57vs1.57±0.26,均P<0.01),其中联合治疗组变化最为明显.结论:阿苯哒唑脂质体与槐耳浸膏联合用药可以明显增强小鼠免疫功能,抑制细粒棘球蚴的生长,使小鼠肝细粒棘球蚴病术后感染率降低.

AIM： To explore the inhibition of different grugs on the hepatic echinococcus granulosus infection in mice, and to investigate the influence on the infection after enhancing the host immune function. METHODS： After immunization with echinococcus granulosus cyst fluid for 3 wk, mice with positive IgG seroresponses were divided into drug-treated group and model control group. One week before infection and one month after infection with prostoscolex, the mice in the former were treated with single liposomal albendazole （L-Alb）, single huaier extract, and huaier extract with L-Alb, respectively. The prostoscolex was dealed with 750 mL/L alcohol, 200 g/L hypertonic saline, L-Alb and balanced solution when the mice were inoculated. After infection for 90 d, the pathological changes, spleen index, the levels of IgG and IgE in peripheral blood were observed; meanwhile, the levels of CD4^± and CD8^± cells were determined by flow cytometry. RESULTS： Pathological examination showed that the germinal layer and corneous layer of echinococcus granulosus were severely damaged in the mice with combined treatment. There were significant differences in the spleen index and the levels of serum IgE between the drugtreated groups and the model control group （3.84 ± 0.86, 3.95 ± 1.01, 3.27 ± 0.52 vs 5.46 ± 0.52; 0.06 ± 0.08μg/L, 0.07 ± 0.08 μg/L, 0.03 ± 0.03μg/L vs 0.20 ± 0.02μg/L; all P 〈 0.01）; the difference was the most significant between the combined treatment group and the model control group. The level of IgG had no marked difference between the drug-treated groups and the model control group. The level of CD8~ cells was significantly lower （16.60 ± 3.89, 18.18 ± 3.90, 15.38 ± 2.63 vs 32.90 ± 4.71; all P 〈 0.01）, but the level of CD4^＋/ CD8^＋ cells was higher （3.21 ± 0.70, 3.05 ± 0.66, 3.53 ± 0.57 vs 1.57 ± 0.26; all P 〈 0.01） in the drugtreated groups than that in the model control group; the most significant change was observed in the mice with combined treatment. CONCLUSION： L-Alb combined with huaier extract may obviously enhance immune function, inhibit the growth of echinococcus granulosus, and reduce the post-operative infection of echi- nococcus granulosus in mice.