目的通过制备氯磷酸二钠脂质体(LE-Cl2MDP),选择性剔除日本血吸虫感染小鼠模型中Kupffer细胞,研究抑制Kupffer细胞功能对日本血吸虫肝脏肉芽肿形成的影响。方法采用脂质体包裹CL2MDP;6~8周龄雌性BALB/c小鼠分为3组:PBS组,日本血吸虫感染组,日本血吸虫感染联合LE-Cl2BMP组;对于联合组,小鼠尾静脉注射LE-Cl2MDP(0.1mL/10g),每周2次,连续6周;感染后第12周,剥杀小鼠,留取血清及肝脏,用于细胞因子和免疫组织化学检测等,数据统计分析。结果经过LE-Cl2MDP处理后,日本血吸虫感染肉芽肿周围Kupffer细胞细胞明显减少;无论是感染第8周,还是第12周肝组织中虫卵肉芽肿周围炎症细胞浸润明显减少,纤维化程度减轻;同时降低感染第12周小鼠血清IL-10水平,LE-Cl2MDP组为(42.6±10.4)pg/mL,感染组为(67.4±12.9)pg/mL(P〈0.05)。结论本研究建立LE-Cl2MDP剔除小鼠肝脏Kupffer细胞的日本血吸虫感染模型,抑制了肝组织中虫卵肉芽肿周围炎症反应。
Liposome-encapsulated dichloromethylene diphosphonate (LE-C12 MDP) was prepared to selectively eliminate out Kupffer cells in a mouse model of Schistosoma japonica infection. Further studies by inhibiting the effects of Kupffer cell func- tion were implemented to judge whether it impacted on the liver granuloma formation of Schistosoma japonica infection. Lipo- some was used to package CL2 MDP. The 6-8 weeks old female BALB/c mice were divided into three groups, including phos- phate buffered saline (PBS) group, Schistosoma japonica infection group and Schistosoma japonica infection combined LE-Clz BMP group. The combination group model was reproduced by injection of LE-C12 BMP into tail vein (0.1 mL/10 g) for twice a week through six weeks. Mice were sacrificed at 12 week post infection with Schistosoma japonicum, serum and liver speci- mens were collected to detect eytokines and immunohistoebemistry, etc. Statistical analysis was performed based on relevant data. Results showed that after LE-ClzMDP treatment, Kupffer cells of Schistosoma japonica egg granuloma significantly re- duced. Inflammatory cells infiltration surrounding schistosome egg granuloma in liver also decreased significantly, and that alle- viated hepatic fibrosis at 8 or 12 week. At 12 weeks after infection, the level of IL-10 in the sera of the mice with schistosomia- sis infection combined LE-C12 MDP group (42. 6 10.4) pg/mL was significantly lower than that of schistosomiasis infection group (67.4 12.9) (P〈0.05). This study established the model that LE-C12MDP was able to eliminate the hepatic Kupffer cells in the mice infected with Schistosoma japonicurn, and it also inhibited inflammatory response around schistosomal egg granuloma.