透皮增强肽TD1与表皮生长因子融合蛋白功能的研究

发布时间：2018-03-26 01:03

本文选题：TD1　切入点：透皮给药　出处：《中国科学技术大学》2011年硕士论文

【摘要】：透皮给药相对于传统的口服与皮下注射给药方式而言,其具有方便性、可持续性和可控制性强等优点。近年来,透皮给药的研究与应用为治疗疾病的给药方式提供了新的途径。 TD1是一个具有11个氨基酸的短肽(ACSSSPSKHCG),其能够通过简单混合涂抹给药的方式促进胰岛素等蛋白大分子药物透过皮肤到达动物体血液循环中而发挥治疗作用。本文中我们利用分子生物学方法使TD1通过GGGGS共价连接至EGF的N端,得到了TD1-EGF融合蛋白。我们发现TD1-EGF与普通的EGF相比,具有类似的促细胞生长、迁移与刺激ERK1/2磷酸化激活的细胞活性,且比普通的EGF更容易透过完整的动物皮肤。TD1-EGF的促透作用具有明显的时间与浓度依赖性,并且这种显著的促透效果需要正常的体温条件。这可能是TD1与皮肤间存在相互作用而并非与药物作用的结果。通过本文对TD1-EGF的细胞活性与透皮活性的研究,为TD1-EGF在经皮给药、损伤修复以及医疗美容等领域的应用提供了理论基础。
[Abstract]:Compared with the traditional oral and subcutaneous administration, transdermal administration has the advantages of convenience, sustainability and controllability. In recent years, the research and application of transdermal drug delivery have provided a new way for the treatment of diseases. TD1 is a short peptide with 11 amino acids, ACSSSPSKHCG, which can promote insulin and other protein macromolecular drugs through the skin to reach the blood circulation of animal body and play a therapeutic role. We used molecular biology to coconnect TD1 to the N-terminal of EGF via GGGGS. TD1-EGF fusion protein was obtained. We found that TD1-EGF has similar cellular activity to promote cell growth, migrate and stimulate phosphorylation of ERK1/2, as compared with normal EGF. Moreover, the permeation effect of TD1-EGF through intact animal skin was more obvious in a time-and concentration-dependent manner than that of normal EGF. And this remarkable penetration effect requires normal body temperature conditions, which may be the result of interaction between TD1 and skin rather than drugs. The study on the cellular and transdermal activity of TD1-EGF provides a theoretical basis for the application of TD1-EGF in the field of transdermal drug delivery, injury repair, medical beauty and so on.
【学位授予单位】：中国科学技术大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R346

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