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文章摘要
融合蛋白HSA-HGF的体内抗肝纤维化活性研究
Study on the anti-liver fibrosis activity of HSA-HGF in vivo
投稿时间:2019-07-18  修订日期:2019-08-07
DOI:
中文关键词: 肝细胞生长因子  人血清白蛋白融合蛋白  肝纤维化
英文关键词: hepatocyte growth factor  human serum albumin fusion protein  liver fibrosis
基金项目:国家高技术研究发展计划(863计划)
作者单位E-mail
蔡燕飞 江南大学 xinlangone@163.com 
徐栋生 江南大学  
陈蕴 江南大学  
金坚 江南大学 jinjian31@126.com 
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中文摘要:
      肝细胞生长因子(hepatocyte growth factor, HGF)在治疗肝纤维化过程中扮演着重要角色,但其在血液循环中并不稳定,半衰期短,提高HGF在血液循环中的稳定性是HGF应用性研究的重要内容。本研究在课题组前期研究的基础上,对人血清白蛋白(human serum albumin,HSA)融合蛋白HSA-HGF的体内抗肝纤维化能力进行了研究分析。通过 CCl4 诱导构建小鼠肝纤维化模型,并设置(1)正常组;(2)模型组;(3)阳性组;(4)HSA组;(5)HGF治疗组;(6)HSA-HGF治疗组。经过苏木素-伊红染色、Masson染色、血清肝功能指标活性检测、qRT-PCR法检测肝组织中α-SMA和COLⅠ基因转录水平、TRFIA法检测体内半衰期,从而鉴定各组抗肝纤维化效果。结果显示:(1)运用 CCl4构建肝脏损伤小鼠模型,药物作用后结果显示融合蛋白HSA-HGF及其单体药物均可以明显促进小鼠的肝脏恢复;(2)与单体药物相比,融合蛋白HSA-HGF在降低给药频率的情况下能取得相当的治疗效果;(3)小鼠体内半衰期分析显示,融合蛋白的体内半衰期由单体的3 min增加到3 h左右。表明融合蛋白HSA-HGF具有明显的抗纤维化效果,与单体药物相比,融合蛋白药物的半衰期明显延长,表明该融合蛋白稳定性更佳,具有成为抗肝纤维化药物的潜力。
英文摘要:
      The hepatocyte growth factor (HGF) plays an important role in the treatment of liver fibrosis, but the instability and short half-life it is not stabl in blood circulation limit its application. Thus, great efforts have been invested to improve the stability of HGF. Based on the preliminary research, this study is devoted to the study of the anti-liver fibrosis activity in vivo of human serum albumin (HSA) fusion protein HSA-HGF. Firstly, the mice were randomly divided into the following groups: (1) control; (2) liver fibrosis model; (3) positive control; (4) HSA group; (5) the treatment group of HGF; (6) the treatment group of HSA-HGF. And the mice liver fibrosis models were constructed by CCl4 induction. Secondly, the anti-fibrosis effects were determined by hematoxylin eosin staining, masson staining, serum liver function index activity detection, qRT-PCR detection of α-SMA and COL I, and TRFIA detection of Half-Life in vivo. Finally, the results indicated that: (1) the fusion protein and its monomer drug could both significantly promote liver recovery of the mice liver fibrosis model; (2) Compared with the monomer drug, the fusion protein still maintained the significant anti-fibrosis effect even at low injection frequency; (3) the half-life of this fusion protein remarkably increased from 3 min to 3 h in vivo. Our study indicated that the HSA-HGF fusion protein could provide the capability for liver protection and anti-fibrosis, and the fusion protein shows higher stability and a longer half-life than the monomer drug. In general, the HSA-HGF fusion protein would be a potential drug for the treatment of liver fibrosis.
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