IL-6RFP在小鼠血吸虫感染中对肝细胞的保护作用  

IL-6RFP can protect liver function in the model of mice infected with Schistosoma japonicum

作　　者：平春光 程海燕[1] 高闻达 计永胜[1] 刘淼[1] 任翠平[1] 邵延靖 华梦晴 沈际佳[1] 

机构地区：[1]安徽医科大学病原生物学教研室,合肥230032 [2]美国安泰吉生物技术与制药有限公司,波士顿02118

出　　处：《安徽医科大学学报》2015年第11期1538-1542,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:30972569;81471982)

摘　　要：目的探讨鼠白介素6受体融合蛋白(m IL-6RFP)在BALB/c小鼠日本血吸虫感染模型中对肝细胞的保护作用。方法通过亲和层析方法获得可阻断白介素-6(IL-6)的m IL-6RFP,经人类肝癌细胞(Hep G2)IL-6刺激及阻断实验检测纤维蛋白原(fibrinogen,FGG)和结合珠蛋白(haptoglobin,HP)的mRNA表达变化,体外验证重组蛋白m IL-6RFP的生物活性。建立BALB/c小鼠日本血吸虫感染模型,于感染第24天起经尾静脉注射m IL-6RFP,隔天注射每次100μg/只,感染第42天剖杀小鼠。HE染色法检测小鼠肝脏肉芽肿面积,荧光定量PCR法检测小鼠肝组织IL-1β、IL-13、肿瘤坏死因子-α(TNF-α)和趋化因子1(CXCL1)的mRNA表达,连续监测法检测小鼠肝功能指标谷丙转氨酶(ALT)和谷草转氨酶(AST)。结果 Hep G2细胞实验显示m IL-6RFP可降低IL-6对该细胞的刺激作用,显著下调FGG和HP的表达(P<0.05)。在小鼠感染模型中阻断IL-6后,肝功能指标ALT和AST与溶剂对照组相比均显著下降(P<0.05),肉芽肿病变无显著性差异。结论在BALB/c小鼠日本血吸虫感染模型中m IL-6RFP可明显改善肝细胞功能,但对肉芽肿形成未见明显作用。Objective To explore the role of mouse interleukin-6 receptor fusion protein（ m IL-6RFP） for the protection of liver cells in the model of BALB / c mice infected with Schistosoma japonicum. Methods Nickel ion column was used to obtain purified recombinant m IL-6RFP protein. In vitro,Hep G2 cells were used to verify the biological activity of m IL-6RFP. BALB / c mice were administrated by tail vein injection with 100 μg of m IL-6RFP or equal volume solvent,at 24,26,28,30,32,34,36,38,and 40 days after infection. Mice were sacrificed 48 h after the last injection. The granuloma size was measured in the mouse liver by HE staining. Interleukin-1β（ IL-1β）,interleukin-13（ IL-13）, tumor necrosis factor-α（ TNF-α） and chemokine（ C-X-C motif） ligand 1（ CXCL1） mRNA levels in mouse liver tissue were detected by RT-PCR. Alanine aminotransferase（ ALT） and aspartate transaminase（ AST） were measured by the continuous monitoring method. Results Hep G2 cells experiments showed that m IL-6RFP could reduce the effect of IL-6 on Hep G2 cells,fibrinogen（ FGG） and haptoglobin（ HP） was significantly reduced（ P〈0. 05）. In the BALB /c mice infected with Schistosoma japonicum,when IL-6 was blocked the levels of ALT and AST were decreased significantly（ P〈0. 05） compared with that of the solvent group,while there was no significant difference on granuloma formation. Conclusion In the BALB / c mice infected with Schistosoma japonicum,m IL-6RFP can significantly improve the liver function but no obvious effect on granuloma formation.

关 键 词：IL-6 日本血吸虫 BALB/C小鼠 

分 类 号：R383.24[医药卫生—医学寄生虫学] R392.3[医药卫生—基础医学]