血管活性肠肽的研究进展

Research Progress in Vasoactive Intestinal Peptide

血管活性肠肽(Vasoactive intestinal peptide,VIP)是由28个氨基酸组成的直链阳离子神经肽,相对分子质量为3323。VIP作为神经内分泌激素、神经递质和细胞因子在体内产生多种重要的生物效应,如舒张血管、促进胃肠蠕动、调节免疫和保护中枢等。对动物模型的研究表明,VIP对多种疾病有治疗潜力,如以VIP脂质体、纳米粒药物、重组质粒、基因治疗等方式给药可明显改善病变特征。因此,以VIP为基础进行药物的研究开发具有一定的理论依据和广阔的应用前景。但是,目前把VIP开发成药仍存在很大阻力,主要是VIP代谢不稳定,易被酶解,生物作用复杂。文章综述了VIP的分子特征、VIP受体(VPAC)的介导方式、VIP的生物学作用和VIP的成药展望,并结合作者的工作,提出了对VIP进行结构修饰的设想。

Vasoactive intestinal peptide （VIP） is a linear cationic neuropeptide containing 28 amino acids, and its molecular weight is 3323. VIP exhibited a wide range of biological functions as a neuroendocrine hormones, neurotransmitter and cytokines, including relaxing vessels, promoting gastric peristalsis, modulating the immune system and protecting the central nervous system. The study on animal models demonstrated that VIP was an attractive therapeutic candidate. The pathological characters of models were distinctly improved after treating with VIP in the form of liposome, nanoparticle, recombinant plasmid or VIP gene. Therefore,it becomes relia- ble theoretical basis and has expansive application prospect to develop VIP or its derivates toward the potential drugs. However some obstacles still exist between the laboratory and the clinic ,mainly because of its structural unstability, high sensitivity to protease deg- radation and complex biological actions. To comprehensively understand the research methods and progresses of VIP, its molecular characters, the mediated processes of VIP receptors （VPAC） , its biological functions and prospective of developing it toward drugs are reviewed. In addition, some suggestions on modification of VIP to make it more stable are proposed based on the author＇s work.