Sorafenib联合吡喹酮对日本血吸虫病小鼠肝纤维化病理学的作用

Effects of Sorafenib combined with Praziquantel on hepatic fibrosis pathology of mice with schistosomiasis japonica

目的观察Sorafenib在吡喹酮杀虫基础上对小鼠日本血吸虫病肝纤维化病理形态学的作用。方法 65只小鼠经腹壁感染日本血吸虫尾蚴,8周后形成血吸虫病肝纤维化模型,随机分为感染组(10只)、Sorafenib组(15只)、吡喹酮组(20只)和吡喹酮联合Sorafenib组(20只),另设正常对照组(5只)并分组给药。吡喹酮组:150 mg/(kg·d),连续治疗2天后给予等量生理盐水灌服2周;Sorafenib组:2天生理盐水灌服(剂量同吡喹酮组)后给予Sorafenib 2 mg/(kg·d),每日1次,灌服2周;吡喹酮联合Sorafenib组:吡喹酮150 mg/(kg·d),治疗2天后给予Sorafenib 2 mg/(kg·d),每日1次,灌服2周。正常组及感染对照组自给药开始每日1次灌服等量生理盐水至实验结束。处死小鼠后取肝脏,观察肝脏形态并取部分肝组织作病理学检查。应用HE染色观察小鼠肝脏的病理改变,Masson染色观察肝组织胶原纤维沉积范围,并采用IPP 6.0图文分析软件定量计算胶原纤维相对面积以反映纤维化程度。结果吡喹酮联合Sorafenib组小鼠肝脏病理损害明显减轻,纤维范围显著减少,该组胶原纤维相对面积(1.86±0.87)与感染组(5.97±1.77)和吡喹酮组(3.78±1.08)比较差异有统计学意义(P<0.0001),单用Sorafenib组胶原纤维相对面积(5.51±1.11)与感染组比较差异无统计学意义(P=0.42)。结论 Sorafenib在吡喹酮杀虫基础上能减轻日本血吸虫病肝脏病理损伤,二者联合有显著的增效作用。

Objective To evaluate the effects of Sorafenib combined with Praziquantel on hepatic fibrosis pathology of mice with schistosomiasis japonicum. Methods After infected with schistosoma japonicum cercaria percutaneously through the abdomen for 8 weeks, total of 65 mice formed schistosomiasis liver fibrosis model, and were randomly divided into infected group（10 cases）, Sorafenib group（15 cases）, Praziquantel group（20 cases） and Sorafenib combined with Praziquantel group（20 cases）. Five normal mice were taken as the control group. Drug treatment was given immediately. Praziquantel group was treated with Praziquantel 150 mg/（kg·d） for 2 days and continued to be given equivalent normal saline solution once a day for 2 weeks. Sorafenib group was treated with equivalent normal saline solution once a day for 2 days and continued to be treated with Sorafenib 2 mg/（kg·d） once a day for 2 weeks. Sorafenib combined with Praziquantel group was treated with Praziquantel at the same dose for 2 days followed by treatment with Sorafenib 2 mg/（kg·d） for 2 weeks. The control group and infected group were treated with equivalent normal saline solution from the beginning of drug delivery to the end of the experiment. After the mice in each group were sacrificed, the fresh liver tissues were observed, while parts of the liver were used for HE staining and Masson staining to observe the pathological changes and fibrosis extent. Image-Pro Plus 6.0 software was applied to calculate collagen fiber relative area quantitatively which showed fibrosis extent. Results In Sorafenib combined with Praziquantel group, pathological damage of mice liver reduced significantly and fibrosis extent relieved obviously. There was significant difference when collagen area in Sorafenib combined with Praziquantel group（1.86 ± 0.87） was compared with that in Praziquantel group（3.78 ± 1.08） and infected group（5.97 ± 1.77）（P 〈0.0001）. But the difference was not statistically significant between infected group and Sorafenib group（5.51 ± 1.11）（P = 0.42）. Conclusion On the basis of Praziquantel insecticide, Sorafenib can reduce liver pathological damage in mice with Schistosoma japonicum, and the effect of Sorafenib combined with Praziquantel on anti-fibrosis is reinforced cooperatively.