紧密连接广泛存在于上皮细胞间和内皮细胞间,能够调控旁细胞途径的物质转运并维持细胞极性。其中,肠上皮细胞间的紧密连接可阻止各种抗原渗漏至血液循环, 维持机体稳态, 而这一机制的破坏可能导致多种肠道以及肠外疾病。连蛋白作为肠上皮紧密连接开放剂,其水平升高是乳糜泻等肠道疾病发生的早期事件,而醋酸拉唑肽(larazotide acetate, 亦称AT-1001)是连蛋白竞争性抑制剂, 已有体外实验和临床试验表明AT-1001可有效稳定紧密连接复合物的结构、增强屏障功能,缓解由紧密连接屏障功能破坏所引起的疾病的发生和发展。本文重点综述了AT-1001的作用机制及近年来在乳糜泻等多种疾病中应用的研究,为AT-1001未来的临床应用提供了全面的认识。

Tight junctions are widely present between epithelial cells and endothelial cells, which can regulate the transport of substances through paracellular pathways and maintain cell polarity. Among them, the tight junctions between intestinal epithelial cells can prevent various antigens from leaking into the blood circulation and maintain the body’s homeostasis, the disruption of which may lead to a variety of intestinal and extraintestinal diseases. The elevated level of zonulin, an intestinal epithelial tight junction opener, serves as an early event in intestinal diseases such as celiac disease. Larazotide acetate (also known as AT-1001), a competitive inhibitor of zonulin, has been shown by in vitro studies and clinical trials to effectively stabilize the structure of tight junction complexes, enhance barrier functions, and alleviate the occurrence and development of diseases caused by the breakdown of tight junction barrier functions. This review focuses on the mechanism of action of AT-1001 and its application in the treatment of various diseases such as celiac disease, providing a comprehensive understanding of the future clinical application of AT-1001.