Carpani de Kaski M, Rentsch R, Levi S, Hodgson H J
Department of Medicine, Hammersmith Hospital, London.
Gut. 1995 Nov;37(5):613-6. doi: 10.1136/gut.37.5.613.
The association between corticosteroid treatment and gastric ulcer healing is controversial. The effects of corticosteroids on experimental ulcer healing in the rat were studied and the effect of coadministration of a prostaglandin E1 analogue was determined. Forty male adult rats were divided into five groups and pretreated for 10 days as follows: (a) control, (b) prednisolone (10 mg/kg), (c) prednisolone and misoprostol (300 micrograms/kg), (d) misoprostol, and (e) indomethacin (2 mg/kg) Gastric ulcer was induced by applying a cryoprobe to the serosal surface of the stomach. Healing was assessed by determining the ulcer size at three and six days. Mucosal regenerative activity at the ulcer edge was assessed by quantitating DNA synthesis in cells by immunohistochemical techniques using monoclonal antibodies to detect expression of proliferating cell nuclear antigen (PCNA) and incorporated 5-bromo-5-iododeoxyuridine (BrdU). Compared with control rats, the rate of healing and the mucosal regenerative activity were significantly reduced in rats treated with prednisolone and indomethacin (p < 0.05). Coadministration of misoprostol and corticosteroids reversed the delay in healing and the reduction in mucosal regeneration induced by corticosteroids alone. With misoprostol alone, the ulcer size and the number of epithelial cells that actively synthesised DNA did not differ from control animals. A comparison between the two immunohistochemical markers of cell proliferation showed a highly significant correlation between the two techniques (r = 0.64, p < 0.005), indicating that the simpler PCNA technique should prove valuable in assessing regeneration in experimental ulcer disease.
皮质类固醇治疗与胃溃疡愈合之间的关联存在争议。本研究探讨了皮质类固醇对大鼠实验性溃疡愈合的影响，并确定了联合使用前列腺素E1类似物的效果。将40只成年雄性大鼠分为五组，进行如下10天的预处理：(a)对照组；(b)泼尼松龙（10毫克/千克）；(c)泼尼松龙与米索前列醇（300微克/千克）；(d)米索前列醇；(e)吲哚美辛（2毫克/千克）。通过将冷冻探头应用于胃浆膜表面诱导胃溃疡。通过在第3天和第6天测定溃疡大小来评估愈合情况。使用单克隆抗体通过免疫组织化学技术检测增殖细胞核抗原（PCNA）的表达和掺入的5-溴-5-碘脱氧尿苷（BrdU），对溃疡边缘的黏膜再生活性进行定量评估。与对照大鼠相比，泼尼松龙和吲哚美辛治疗的大鼠愈合率和黏膜再生活性显著降低（p<0.05）。米索前列醇与皮质类固醇联合使用可逆转单独使用皮质类固醇引起的愈合延迟和黏膜再生减少。单独使用米索前列醇时，溃疡大小和积极合成DNA的上皮细胞数量与对照动物无差异。两种细胞增殖免疫组织化学标记物之间的比较显示，两种技术之间存在高度显著的相关性（r = 0.64，p<0.005），这表明更简单的PCNA技术在评估实验性溃疡疾病的再生方面应具有价值。
