无金属黑色素纳米酶用于肝纤维化治疗  

Metal-free Melanin Nanoenzymes for the Treatment of Liver Fibrosis

作　　者：李婷婷[1,2] 岳彩凤[1] 霍媛青 纪慧芳 张瑞平 LI Tingting;YUE Caifeng;HUO Yuanqing;JI Huifang;ZHANG Ruiping(College of Pharmacy,Shanxi Medical University,Taiyuan 030001,China;the Third Hospital of Shanxi Medical University,Shanxi Bethune Hospital,Shanxi Academy of Medical Science,Tongji Shanxi Hospital,Taiyuan 030032,China;The Radiology Department of Shanxi Provincial People’s Hospital,the Fifth Hospital of Shanxi Medical University,Taiyuan 030012,China)

机构地区：[1]山西医科大学药学院,太原030001 [2]山西医科大学第三医院,山西白求恩医院,山西医学科学院,同济山西医院,太原030032 [3]山西省人民医院放射科,山西医科大学第五医院,太原030012

出　　处：《高等学校化学学报》2024年第1期24-32,共9页Chemical Journal of Chinese Universities

基　　金：中国博士后科学基金(批准号:2022M722001);山西省自然科学研究面上项目(批准号:202103021224241);山西医科大学校博士启动基金(批准号:03201529)资助.

摘　　要：以5,6-二羟基吲哚为单体,通过自由基聚合反应合成了无金属黑色素纳米酶(MeNPs),并探究了其治疗肝纤维化的作用.结果表明,MeNPs纳米酶为单分散球形结构,粒径为(91.3±2.6)nm,具有类超氧化物歧化酶(SOD)和类过氧化氢酶(CAT)活性,其催化活性遵循典型的Michaelis-Menten动力学,Michaelis-Menten常数(Km)和最大反应速度(V_(max))分别为1.01 mmol/L和8.49×10^(−6)mol/(L·s).细胞计数试剂盒(CCK-8)等体外细胞实验结果证实MeNPs对H_(2)O_(2)诱导的氧化应激具有细胞保护作用.经MeNPs纳米酶治疗的肝纤维化小鼠的炎症因子IL-6,TNF-α,IL-1β和趋化因子CXCL-1水平显著降低;肝脏损伤指标ALT,AST和肝组织H&E染色均显示MeNPs干预肝纤维化的良好疗效.本文研究结果对于构建安全、高效的自由基清除纳米酶具有一定的指导意义,也为肝纤维化的治疗提供了理论依据和物质基础.Metal-free Melanin nanoenzymes(MeNPs)were synthesized via the free radical polymerization of 5,6-dihydroxyindole as monomer,and its therapeutic effect on liver fibrosis was explored.The results showed that the MeNPs nanoenzymes had monodisperse spherical structure with a particle size of(91.3±2.6)nm,with superoxide-like dismutase(SOD)and catalase-like(CAT)activities,and their catalytic activities followed typical Michaelis-Menten kinetics with Michaelis-Menten constant(Km)and maximum reaction velocity(Vmax)of 1.01 mmol/L and 8.49×10^(−6)mol/(L·s),respectively.In vitro cell experiments such as cell counting kit-8(CCK-8)confirmed that MeNPs had cytoprotective effects on H2O2-induced oxidative stress.Inflammatory factors IL-6,TNF-α,IL-1βand chemokine CXCL-1 were significantly reduced in the mouse model of liver fibrosis treated by MeNPs nanoenzymes.Liver damage indexes ALT,AST and H&E staining of liver tissue showed the good efficacy of MeNPs in liver fibrosis.The research has guiding significance for the construction of safe and efficient free radical scavenging nanoenzymes,and also provides a theoretical basis and material basis for the treatment of liver fibrosis.

关 键 词：黑色素 无金属纳米酶 类超氧化物歧化酶 类过氧化氢酶 肝纤维化 

分 类 号：O623[理学—有机化学] R313[理学—化学]