期刊名：Scientific Reports日期：2016-05-19
DOI：10.1038/srep25672 中國科研用戶發表 作者：馬興元、陸一鳴
2016年5月9日，國際學術權威刊物自然出版集團旗下子刊《Scientific Reports》在線發表了華東理工大學生物反應器工程國家重點實驗室馬興元教授研究組和第二軍醫大學陸一鳴教授研究組合作關於生物技術創新藥物研究的一項研究成果，碩士研究生鄭增節為論文共同第一作者之一，馬興元教授和陸一鳴教授為論文共同通訊作者。
本次研究獲得了一種主要針對炎性相關疾病，如癌症、傳染病、關節炎等抗炎治療的新型生物活性多肽H-SN1，並闡釋了其作用的分子機制，為進一步將其研發為治療上述疾病的新藥奠定了重要基礎。
炎性反應是感染性疾病和腫瘤病人中多伴發的一種常見的病理現象，因此，抗炎性治療是防治傳染病、腫瘤等炎性相關疾病的重要手段。傳統的抗生素和化療藥物由於選擇性差，且易產生毒副作用和耐藥性，而生物技術藥物在這方面具有明顯優勢。本研究利用高通量篩選方法從Hydrophis cyanocinctus蛇毒腺T7噬菌體展示庫中獲得了可與腫瘤壞死因子1(TNFR1)選擇性結合的Hydrostatin-SN1 (H-SN1)多肽分子，經過一系列體外和體內抗炎活性檢測和毒性評判，結果顯示，H-SN1不僅對炎性介導的TNFR1具有高特異性抑制作用，而且經小鼠急性結腸炎模型試驗顯示其具有極低的臨床副作用;同時本研究還對該活性多肽的作用機理進行了研究和闡釋, 其可以通過對胚胎腎細胞HEK293和腺癌HT29細胞系中的TNF-α誘導的NF-кB 和MAPK 激活TNFR1相關的信號通路，並在mRNA和蛋白水平對TNF/TNFR1下游的靶點產生抑制作用。
原文鏈接：
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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