期刊名：Scientific Reports日期：2016-05-19
DOI：10.1038/srep25672 中国科研用户发表 作者：马兴元、陆一鸣
2016年5月9日，国际学术权威刊物自然出版集团旗下子刊《Scientific Reports》在线发表了华东理工大学生物反应器工程国家重点实验室马兴元教授研究组和第二军医大学陆一鸣教授研究组合作关于生物技术创新药物研究的一项研究成果，硕士研究生郑增节为论文共同第一作者之一，马兴元教授和陆一鸣教授为论文共同通讯作者。
本次研究获得了一种主要针对炎性相关疾病，如癌症、传染病、关节炎等抗炎治疗的新型生物活性多肽H-SN1，并阐释了其作用的分子机制，为进一步将其研发为治疗上述疾病的新药奠定了重要基础。
炎性反应是感染性疾病和肿瘤病人中多伴发的一种常见的病理现象，因此，抗炎性治疗是防治传染病、肿瘤等炎性相关疾病的重要手段。传统的抗生素和化疗药物由于选择性差，且易产生毒副作用和耐药性，而生物技术药物在这方面具有明显优势。本研究利用高通量筛选方法从Hydrophis cyanocinctus蛇毒腺T7噬菌体展示库中获得了可与肿瘤坏死因子1(TNFR1)选择性结合的Hydrostatin-SN1 (H-SN1)多肽分子，经过一系列体外和体内抗炎活性检测和毒性评判，结果显示，H-SN1不仅对炎性介导的TNFR1具有高特异性抑制作用，而且经小鼠急性结肠炎模型试验显示其具有极低的临床副作用;同时本研究还对该活性多肽的作用机理进行了研究和阐释, 其可以通过对胚胎肾细胞HEK293和腺癌HT29细胞系中的TNF-α诱导的NF-кB 和MAPK 激活TNFR1相关的信号通路，并在mRNA和蛋白水平对TNF/TNFR1下游的靶点产生抑制作用。
原文链接：
Screening of an anti-inflammatory peptide fromHydrophis cyanocinctus and analysis of its activities and mechanism in DSS-induced acute colitis
原文摘要：
Snake has been used for centuries as a traditional Chinese medicine, especially for therapeutic treatment for inflammatory diseases; however, its mechanisms of action and active constituents remain controversial. In our study, a tumor necrosis factor receptor 1 (TNFR1) selecive binding peptide, Hydrostatin-SN1 (H-SN1), which was screened from a Hydrophis cyanocinctus venom gland T7 phage display library, was shown to exhibit significant anti-inflammatory activity in vitro and in vivo. As a TNFR1 antagonist, it reduced cytotoxicity mediated by TNF-α in L929 fibroblasts and effectively inhibited the combination between TNF-α with TNFR1 in surface plasmon resonance analysis. H-SN1 was also shown to suppress TNFR1–associated signaling pathways as it minimized TNF-α-induced NF-кB and MAPK activation in HEK293 embryonic kidney and HT29 adenocarcinoma cell lines. We next determined the effect of H-SN1 in vivo using a murine model of acute colitis induced by dextran sodium sulfate, demonstrating that H-SN1 lowered the clinical parameters of acute colitis including the disease activity index and histologic scores. H-SN1 also inhibited TNF/TNFR1 downstream targets at both mRNA and protein levels. These results indicate that H-SN1 might represent a suitable candidate for use in the treatment of TNF-α-associated inflammatory diseases such as inflammatory bowel diseases.
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