重组转化生长因子β_1疫苗诱导大鼠产生特异性抗体及其抗肝纤维化作用研究

The Study of the Specific Antibody of Rat Induced by Recombinant TGF-β_1 Vaccine and Its Preventing Hepatic Fibrosis

目的检测重组转化生长因子β1(TGF-β1)疫苗诱导大鼠产生的特异性抗体,探讨其对早期肝纤维化的阻断作用。方法将30只雄性SD大鼠随机分为3组(正常组、模型组和疫苗干预组),各10只。模型组大鼠给予0.5%的二甲基硝胺(按0.2ml/100g)腹腔内注射制备肝纤维化模型;疫苗干预组在注射二甲基硝胺的基础上于大鼠背部皮下注射重组TGF-β1疫苗;正常组大鼠腹腔注射0.9%氯化钠注射液0.2ml/100g。实验4周后处死大鼠,取血清检测抗TGF-β1水平,取肝脏组织做HE染色和Masson染色,比较4组大鼠的肝纤维化分级。结果正常组、模型组、疫苗干预组大鼠血清抗TGF-β1抗体水平分别为(68.0±38.9)、(75.6±23.7)和(848.9±94.8),疫苗干预组大鼠血清抗TGF-β1抗体水平显著高于模型组及正常组,差异有统计学意义(P<0.01),而正常组与模型组大鼠血清抗TGF-β1抗体水平间差异无统计学意义(P>0.05)。与模型组比较,疫苗干预组大鼠纤维化分级显著减轻(P<0.01),但仍与正常组有显著差异(P<0.01)。结论重组TGF-β1疫苗不仅能诱导大鼠产生特异性抗体,而且对早期肝纤维化起到了积极的阻断作用。

Objective To measure the specific antibody of rat induced by recombinant TGF-β1 vaccine and to investigate its mechanism of preventing the early hepatic fibrosis.Methods 30 male Sprague-Dawley rats were divided into three groups（normal group,model group,treatment group） randomly,with each group 10 rats.Rats in model group were injected with DMN of 0.5%（0.2 ml/100 g） to establish model with hepatic fibrosis.Rats in treatment group were injected with recombinant TGF-β1 vaccine in addition to DMN.Rats in normal group were injected with Sodium Chloride of 0.9%（0.2 ml/100 g）.The rats were killed four weeks later.The level of anti-TGF-β1 antibody in the serum were detected and hepatic tissue was respectively observed by Hematoxylin-Eosin staining and Masson staining to compare the fibrosis level in four groups.Results The level of anti-TGF-β1 antibody in normal group,model group and treatment group were （68.0±38.9）,（75.6±23.7） and （848.9±94.8） respectively.The level of anti-TGF-β1 antibody was prominently higher in treatment group than that of in model group and normal group,and the difference was significant（P0.01）.The difference was not significant in the level of anti-TGF-β1 antibody between normal group and model group（P0.05）.Comparing with the model group,the fibrosis level of treatment group was significantly reduced（P0.01）,but was still significantly different from that of normal group（P0.01）.Conclusion NOT only did the recombinant TGF-β1 vaccine induce the rats produce specific antibody,but also blocked the procedure of hepatic fibrosis.