Kokoska E R, Smith G S, Rieckenberg C L, Deshpande Y, Banan A, Miller T A
Theodore Cooper Surgical Research Institute, Department of Surgery, Saint Louis University Health Sciences Center, Missouri 63104, USA.
Dig Dis Sci. 1998 Apr;43(4):806-15. doi: 10.1023/a:1018826416864.
The majority of previous work investigating adaptive cytoprotection has involved in vivo studies, which have suggested that this protective response is in large part mediated by endogenous prostaglandins (PGs). The aim of this study was to investigate adaptive cytoprotection under in vitro conditions in human gastric cells and to better delineate the role of endogenous PGs in this protective response. AGS cells (a human gastric carcinoma cell line) were characterized morphologically and subsequently used for all experiments. Sodium deoxycholate was used as both the mild irritant and the damaging agent, and cell injury was quantified using both a commercial viability/cytotoxicity kit as well as transepithelial permeability studies. Finally, endogenous PG synthesis in response to varying concentrations of deoxycholate was determined. AGS cells were determined to be morphologically similar to gastric mucous cells. Pretreatment of cells with low-dose deoxycholate significantly attenuated injury upon subsequent exposure to damaging concentrations of deoxycholate, and this protection was determined to be dependent upon both concentration and duration of mild irritant exposure. Preincubation of AGS cells with indomethacin reversed protection induced by mild irritant pretreatment and also significantly increased cellular susceptibility to injury. Results of the permeability studies closely paralleled those assessing cell mortality. While deoxycholate exposure increased PG synthesis, the concentrations required were much higher than those needed to initiate protection. Adaptive cytoprotection exists in AGS cells under in vitro conditions independent of intact blood flow, neural innervation, or circulating humoral mediators. While this protection is reversed by indomethacin, it appears that this reversal results from increased cellular injury secondary to diminished basal PGs, rather than inhibition of endogenous PG synthesis.
以往大多数研究适应性细胞保护作用的工作都涉及体内研究，这些研究表明这种保护反应在很大程度上是由内源性前列腺素（PGs）介导的。本研究的目的是在体外条件下研究人胃细胞中的适应性细胞保护作用，并更好地阐明内源性PGs在这种保护反应中的作用。AGS细胞（一种人胃癌细胞系）经形态学鉴定后用于所有实验。脱氧胆酸钠用作轻度刺激物和损伤剂，使用商业活力/细胞毒性试剂盒以及跨上皮通透性研究对细胞损伤进行定量。最后，测定了不同浓度脱氧胆酸钠刺激下内源性PG的合成情况。经鉴定，AGS细胞在形态上与胃黏液细胞相似。用低剂量脱氧胆酸钠预处理细胞可显著减轻随后暴露于损伤浓度脱氧胆酸钠时的损伤，且这种保护作用取决于轻度刺激物暴露的浓度和持续时间。用吲哚美辛预孵育AGS细胞可逆转轻度刺激物预处理诱导的保护作用，还显著增加细胞对损伤的敏感性。通透性研究结果与评估细胞死亡率的结果密切平行。虽然脱氧胆酸钠暴露会增加PG的合成，但所需浓度远高于引发保护作用所需的浓度。在体外条件下，AGS细胞中存在适应性细胞保护作用，且不依赖于完整的血流、神经支配或循环体液介质。虽然这种保护作用可被吲哚美辛逆转，但这种逆转似乎是由于基础PGs减少导致细胞损伤增加所致，而非内源性PG合成受到抑制。
