Zhao Nan, Feng Zhaolong, Shao Meng, Cao Jichao, Wang Fengshan, Liu Chunhui
Key Laboratory of Chemical Biology (Ministry of Education), Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
National Glycoengineering Research Center, Shandong University, Jinan 250012, China.
Int J Mol Sci. 2017 May 24;18(6):1121. doi: 10.3390/ijms18061121.
Superoxide dismutase (SOD) has attracted considerable attention on treatment of reactive oxygen species (ROS)-related disorders. We previously conjugated Cu/Zn SOD to -quaternary chitosan derivatives (-HTCC) to yield a polymer-enzyme conjugate -HTCC-SOD that demonstrated superior therapeutic effect to native SOD. The present study demonstrated that -HTCC-SOD had wider pH activity range, better thermal stability, excellent long-term stability for storage, as well as unique reinstatement of activity exposure to proteolytic degradation that was helpful for longer half-life in vivo. -HTCC-SOD exerted significant anti-inflammatory effects on lipopolysaccharides (LPS)-stimulated mouse peritoneal macrophages by down-regulating production of pro-inflammatory cytokines and intracellular ROS. -HTCC-SOD significantly attenuated dextran sodium (DSS)-induced colitis in mice as observed by the colitis severity, neutrophil infiltration and histopathological damage, whereas native SOD failed to do so. In conclusion, conjugation of -HTCC conferred SOD with better stability and enhanced therapeutic potential, offering a promising option in treatment of inflammatory bowel disease.
超氧化物歧化酶（SOD）在治疗活性氧（ROS）相关疾病方面已引起了广泛关注。我们之前将铜/锌超氧化物歧化酶与季铵化壳聚糖衍生物（HTCC）偶联，得到了一种聚合物 - 酶偶联物HTCC - SOD，其显示出比天然SOD更优异的治疗效果。本研究表明，HTCC - SOD具有更宽的pH活性范围、更好的热稳定性、出色的长期储存稳定性，以及在暴露于蛋白水解降解时独特的活性恢复能力，这有助于其在体内具有更长的半衰期。HTCC - SOD通过下调促炎细胞因子和细胞内ROS的产生，对脂多糖（LPS）刺激的小鼠腹腔巨噬细胞发挥显著的抗炎作用。从结肠炎严重程度、中性粒细胞浸润和组织病理学损伤观察，HTCC - SOD显著减轻了葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎，而天然SOD则未能做到这一点。总之，HTCC与SOD的偶联赋予了SOD更好的稳定性并增强了治疗潜力，为炎症性肠病的治疗提供了一个有前景的选择。
