一种新型抗纤维化小肽AcSDKP的构建及活性初步研究  

A Novel AcSDKP Peptide with Anti-Fibrosis Activities In Vivo

作　　者：张昭[1,2] 黄同列[1,2] 徐天娇[1,2] 赵薇[1,2] 李萌[1,2] 张伟 张英起[1,2] 

机构地区：[1]肿瘤生物学国家重点实验室 [2]第四军医大学药学系生物制药学教研室,陕西西安710032

出　　处：《生物技术通讯》2012年第2期158-161,共4页Letters in Biotechnology

摘　　要：目的:以D型氨基酸替代的方式构建一种能抵抗血管紧张素转化酶(ACE)降解的异构体小肽AcSDKP,并对其抗纤维化活性进行初步研究,以期为AcSDKP在抗纤维化方面的应用提供依据。方法:用HPLC法检测D型氨基酸替代方式构建的AcSDKP异构体抗ACE降解的能力;用MTT法检测AcSDKP异构体对小鼠成纤维细胞L929和原代培养的心脏成纤维细胞增殖的影响;用流式细胞术检测AcSDKP异构体对骨髓干细胞(BMSC)向巨噬细胞分化的影响。结果:AcSDKP异构体均能抗ACE降解,能抑制L929细胞和心脏成纤维细胞增殖,能抑制BMSC向巨噬细胞分化。结论:构建了能抵抗ACE降解,在体外能抑制成纤维细胞增殖、巨噬细胞分化的AcSDKP异构体小肽,为该小肽进一步的体内研究及应用奠定了基础。Objective： By D amino acids substitutions, AcSDKP isomers were synthesized for finding an angioten sinconverting enzyme（ACE） resistant peptide. The synthesized candidates were tested in vivo for its biological ac tivity. Methods： Degradation of AeSDKP isomers was measured by HPLC. Proliferation of L929 cells and cardiac fibroblasts were measured by MTT assay. Differentiation of bone marrow stem cells（BMSC） to macrophages was an alyzed by f/ow cytometry using F4/80 as a marker of macrophage maturation. Results： All the three AcSDKP iso mers can resist degradation by ACE. At the concentration of 108 tool/L, AcSDKP isomers inhibited L929 cells pro liferation, cardiac fibroblasts proliferation mediated by TGFI31, and differerntiation of BMSC to macrophages. Con clusion： Successfully obtained the AcSDKP isomers resisting degradation by ACE and having much biological activ ities.

关 键 词：AcSDKP小肽 异构体 抗纤维化 骨髓干细胞 心脏成纤维细胞 

分 类 号：R977.4[医药卫生—药品]