消退素RvE1对日本血吸虫病肝纤维化小鼠外周血肝纤维化指标和细胞因子的影响

Effect of resolvin E1 on serum of cytokines and liver fibrosis index in mice with Schistosomiasis japonica

目的通过检测模型小鼠外周血肝纤维化有关指标和细胞因子水平,研究消退素RvE1对小鼠日本血吸虫病肝纤维化的影响及其机制,从而探讨合理的防治策略。方法用日本血吸虫尾蚴皮肤敷贴法感染小鼠,构建日本血吸虫病肝纤维化模型。感染5w后,将造模组小鼠随机分为2组:模型对照组(血吸虫感染+NS.)、治疗组(血吸虫感染+RvE1),以正常小鼠为正常对照组。感染10w后取血标本,采用放射免疫法检测血清肝纤维化指标,包括Ⅳ型胶原(Ⅳ-C)、Ⅲ型前胶原(PCⅢ)、透明质酸(HA)及层粘连蛋白(LN);留取肝左叶行Masson染色,参照肝纤维化半定量计分系统进行肝纤维化程度评分;采用ELISA法测定RvE1对日本血吸虫病肝纤维化小鼠血清中TNF-α水平的影响。结果感染10w后,各组小鼠未见自然死亡,各组小鼠体重无明显变化,统计学分析无差异;RvE1治疗组小鼠血清肝纤维化各项指标与模型对照组比较均明显降低(P<0.05);与模型对照组比较,RvE1治疗组小鼠肝纤维化评分明显降低(P<0.05);RvE1治疗组小鼠血清中促炎介质TNF-α水平较模型对照组有明显降低(P<0.05)。结论外源性RvE1可发挥抗日本血吸虫病肝纤维化的作用。

To investigate the effect and mechanism of Resolvin E1 on liver fibrosis mice models with Schistosomiasis japonica by detecting the changes of serum levels of cytokines and liver-fibrosis,mice were infected with Schistosoma japonicum cercariae percutaneously,to construct mice models of liver fibrosis of Schistosomiasis japonica.The infected mice were divided randomly into three groups at the end of the 5th week after infection model group,model control group（to inject normal saline）,treated group（to inject RvE1） and normal control group.The mice were killed at the end of the 10th week.The serum level of collagen IV（IV-C）,precollagen Ⅲ（PCⅢ）,hyaluronic acid（HA） and laminin（LN） were evaluated by radioimmunoassay（RIA）.The left liver lobes were examined histopathologically with Masson staining.Grades of hepatic fibrosis were evaluated according to the SSS system.The serum level of TNF-α was evaluated by ELISA.After 10-week infection,no mice died,and the weight of mice was no significant changes in each group.The serum level of liver fibrosis index in RvE1 treated mice,including the C-IV,PCⅢ,HA and LN,were significantly lower than those in the model control group（P 0.05）.Compared with the model control group,liver fibrosis score in RvE1 treated mice was significantly lower（P 0.05）.The serum level of TNF-α in RvE1 treated mice was significantly lower than that in the model control group（P0.05）.RvE1 plays a role in anti-liver fibrosis by anti-inflammatory and promote inflammation subsides in mice with schistosomiasis japonica.