Department of Gastroenterology, Dong A University College of Medicine, Busan, Korea.
J Physiol Pharmacol. 2009 Dec;60 Suppl 7:5-17.
With the discovery of gastric acid and pepsin in the stomach, the questions about "why does the stomach not digest itself?", "how does the stomach preserve its normal integrity under the continuous exposure to lytic materials that are secreted?", and "how does the stomach resist against overwhelming Helicobacter pylori (H. pylori) infection or persistent nonsteroidal anti-inflammatory drugs (NSAID) administration?" had been raised. The discovery of "gastric mucosal barrier" or "the presence of defense system" might be the answers to these questions. The first level of gastric mucosal barrier consists of the factors secreted into the lumen including bicarbonates, mucus, immunoglobulins, other antibacterial substances including lactoferrin, and surface active phospholipids. The second level of defense system is the gastric epithelia, which are remarkably resistant to acids or irritants and forms relatively tight barrier to passive diffusion. In addition, the epithelium is capable of undergoing extremely rapid repair and restitution if its continuity is disrupted. The third level of gastric mucosal barrier is the mucosal microcirculation in concert with sensory afferent nerves within the mucosa and submucosa. Back diffusion of acid or toxin into the mucosa results in neural system-mediated elevations of calcitonin gene related peptide, which contribute to enhancing mucosal blood flows that are very critical for limiting damage and facilitating repair. The fourth level of defense is the mucosal immune system, consisting of mast cells and macrophage, which orchestrate an appropriate inflammatory response to challenge. All the above factors are known to contribute to orchestrated artwork of "gastric mucosal protection". In recent years, heat shock proteins (HSPs) have been implicated to be an additional factor utilized for the gastric defense mechanisms at the intracellular level. Certain HSPs are expressed under non-stressful conditions and play an important role in the maintenance of normal cell integrity, but HSPs are generally considered to improve cellular recovery both by either refolding partially damaged functional proteins or increasing delivery of precursor proteins to important organelles such as mitochondria and endoplasmic reticulum, through which HSPs might complete efficient mucosal defense mechanisms and achieve ulcer healing, mostly probably protecting key enzymes related to cytoprotection. In this review, role of each heat shock protein, HSP90, HSP70, HSP27, in gastric inflammation and gastric ulcer healing will be described with general roles of HSPs.
随着胃酸和胃蛋白酶在胃中的发现，人们提出了“为什么胃不会消化自己？”“在不断暴露于分泌的溶酶物质下，胃如何保持正常完整性？”以及“胃如何抵抗幽门螺杆菌（H. pylori）感染或持续使用非甾体抗炎药（NSAID）的侵袭？”这些问题。“胃黏膜屏障”或“防御系统的存在”的发现可能就是这些问题的答案。胃黏膜屏障的第一道防线由分泌到腔中的物质组成，包括碳酸氢盐、黏液、免疫球蛋白、乳铁蛋白等其他抗菌物质以及表面活性磷脂。第二道防御系统是胃上皮细胞，它对酸或刺激物具有很强的抵抗力，并形成相对紧密的屏障以阻止被动扩散。此外，如果上皮细胞的连续性被破坏，它能够进行极其迅速的修复和恢复。胃黏膜屏障的第三道防线是黏膜微循环与黏膜和黏膜下层的感觉传入神经协同作用。酸或毒素回渗到黏膜会导致神经系统介导的降钙素基因相关肽升高，这有助于增加对限制损伤和促进修复至关重要的黏膜血流量。第四道防线是黏膜免疫系统，由肥大细胞和巨噬细胞组成，它们协调适当的炎症反应以应对挑战。所有这些因素都有助于协调“胃黏膜保护”的艺术。近年来，热休克蛋白（HSPs）被认为是细胞内水平用于胃防御机制的另一个因素。某些 HSP 在非应激条件下表达，在维持正常细胞完整性方面发挥重要作用，但 HSP 通常被认为通过两种方式改善细胞恢复，一种是使部分受损的功能蛋白重新折叠，另一种是增加前体蛋白向重要细胞器（如线粒体和内质网）的输送，通过这种方式，HSP 可能完成有效的黏膜防御机制并实现溃疡愈合，可能主要保护与细胞保护相关的关键酶。在这篇综述中，将描述 HSP90、HSP70、HSP27 等每种热休克蛋白在胃炎症和胃溃疡愈合中的作用，以及 HSP 的一般作用。
