Brzozowski T, Konturek P C, Konturek S J, Ernst H, Stachura J, Hahn E G
Institute of Physiology, Jagiellonian University School of Medicine, Krakow, Poland.
Gut. 1995 Dec;37(6):749-57. doi: 10.1136/gut.37.6.749.
Gastric adaptation to injury during repeated doses of acetyl salicylic acid (ASA) is a well documented finding but it is not known whether this adaptation affects the tolerance of the mucosa to other strong irritants. Gastric adaptation was induced by repeated daily doses of acidified ASA (100 mg/kg in 1.5 ml of 0.2 N HCl) given intragastrically (series A rats). Control rats with an intact stomach were given daily intragastric vehicle only (1.5 ml of 0.2 N HCl) (series B). After full adaptation to ASA (5 days), rats were challenged again with acidified ASA or, for comparison, with strong irritants such as 100% ethanol, 200 mM acidified taurocholate, or 25% NaCl for 1 hour or with water immersion and restraint for 3.5 hours. The first dose of ASA produced numerous gastric lesions and deep histological necrosis accompanied by a fall in the gastric blood flow, negligible expression of epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) or their receptors, and no evidence of mucosal proliferation. As adaptation to ASA developed, however, the areas of gastric lesions were reduced by more than 80% and there was a noticeable decrease in deep necrosis, a partial restoration of gastric blood flow, an approximately four-fold increase in EGF expression (but not in TGF alpha) and its receptors, and an appreciable increase in mucosal cell proliferation compared with vehicle treated rats. Increases in the mucosal expression of EGF receptors and the luminal content of EGF were also found in ASA adapted animals. In ASA adapted rats subsequently challenged with 100% ethanol, 200 mM TC, 25% NaCl, or stress, the area of the gastric lesions and deep histological necrosis were appreciably reduced compared with values in vehicle treated rats. This increased mucosal tolerance to strong irritants was also accompanied by the return of the gastric blood flow towards control levels and further significant increases in the mucosal expression of EGF receptors and mucosal cell proliferation. Gastric adaptation to ASA enhances the mucosal resistance to injury by strong irritants probably as a result of the restoration of the gastric blood flow and increased cell proliferation that may result from increased mucosal expression of EGF and its receptors.
在重复给予乙酰水杨酸（ASA）期间，胃对损伤的适应性是一个有充分文献记载的发现，但尚不清楚这种适应性是否会影响黏膜对其他强刺激物的耐受性。通过每天经胃内给予酸化的ASA（100毫克/千克，溶于1.5毫升0.2N盐酸中）诱导胃适应性（A组大鼠）。胃完整的对照大鼠每天仅给予胃内赋形剂（1.5毫升0.2N盐酸）（B组）。在完全适应ASA（5天）后，大鼠再次接受酸化ASA挑战，或者为作比较，用强刺激物如100%乙醇、200mM酸化牛磺胆酸盐或25%氯化钠处理1小时，或进行3.5小时的水浸束缚处理。首次给予ASA产生了大量胃损伤和深层组织学坏死，伴有胃血流量下降、表皮生长因子（EGF）和转化生长因子α（TGFα）或其受体的表达可忽略不计，且无黏膜增殖迹象。然而，随着对ASA适应性的发展，胃损伤面积减少了80%以上，深层坏死明显减少，胃血流量部分恢复，EGF表达（但TGFα未增加）及其受体增加约四倍，与给予赋形剂处理的大鼠相比，黏膜细胞增殖明显增加。在适应ASA的动物中还发现EGF受体的黏膜表达和EGF的管腔含量增加。在随后用100%乙醇、200mM TC、25%氯化钠或应激挑战的适应ASA的大鼠中，与给予赋形剂处理的大鼠相比，胃损伤面积和深层组织学坏死明显减少。这种对强刺激物的黏膜耐受性增加还伴随着胃血流量恢复到对照水平以及EGF受体的黏膜表达和黏膜细胞增殖进一步显著增加。胃对ASA的适应性增强了黏膜对强刺激物损伤的抵抗力，这可能是由于胃血流量的恢复以及可能由EGF及其受体的黏膜表达增加导致的细胞增殖增加所致。
