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奥美拉唑剂量、非甾体抗炎药及吸烟对急性消化性溃疡出血修复机制的影响

Effect of omeprazole dose, nonsteroidal anti-inflammatory agents, and smoking on repair mechanisms in acute peptic ulcer bleeding.

作者信息

Rantanen Tuomo, Udd Marianne, Honkanen Teemu, Miettinen Pekka, Kärjä Vesa, Rantanen Lassi, Julkunen Risto, Mustonen Harri, Paavonen Timo, Oksala Niku

机构信息

Department of Surgery, Kuopio University Hospital, Box 100, 70029, Kuopio, Finland,

出版信息

Dig Dis Sci. 2014 Nov;59(11):2666-74. doi: 10.1007/s10620-014-3242-z. Epub 2014 Aug 20.

Abstract

BACKGROUND

Peptic ulcer bleeding (PUB) is a major cause of upper gastrointestinal bleeding. The effect of omeprazole on mucosal repair is unknown.

AIMS

We studied the effect of omeprazole, nonsteroidal anti-inflammatory agents, and smoking on PUB.

METHODS

There were 43 PUB patients who received regular or high dose of omeprazole for 72 h. Biopsies from antrum and corpus were taken before and after treatment. Biopsy samples from 20 celiac disease patients worked as controls. The expression of Ki-67, Bcl-2, COX-2, Hsp27, and Hsp70 was analyzed from patients and controls.

RESULTS

Bcl-2 expression in PUB patients was lower than in controls. However, Bcl-2 increased significantly from 5.0 (SD 4.5) to 9.1 % (SD 6.7), p = 0.0004, in the antrum after omeprazole. In univariate analysis, a high omeprazole dose caused a more profound increase in Ki-67 expression in the corpus: 35.3 % (SD 54.8) than a regular dose: -10.1 % (SD 40.6), p = 0.022. In multivariate analysis, Ki-67 decreased significantly in the corpus between the pre- and posttreatment period (p = 0.011), while a high omeprazole dose (p = 0.0265), the use of NSAIDs (p = 0.0208), and smoking (p = 0.0296) significantly increased Ki-67 expression. Bcl-2 in the corpus increased significantly (p = 0.0003) after treatment.

CONCLUSIONS

Our findings suggest that Bcl-2 may be an important factor in the pathogenesis of a peptic ulcer and PUB. In addition, high-dose omeprazole increased the expression of Ki-67, which may enhance the healing process of a peptic ulcer.

摘要

背景

消化性溃疡出血(PUB)是上消化道出血的主要原因。奥美拉唑对黏膜修复的作用尚不清楚。

目的

我们研究了奥美拉唑、非甾体抗炎药和吸烟对消化性溃疡出血的影响。

方法

43例消化性溃疡出血患者接受常规剂量或高剂量奥美拉唑治疗72小时。治疗前后取胃窦和胃体活检组织。20例乳糜泻患者的活检样本作为对照。分析患者和对照中Ki-67、Bcl-2、COX-2、Hsp27和Hsp70的表达。

结果

消化性溃疡出血患者的Bcl-2表达低于对照组。然而,奥美拉唑治疗后胃窦部Bcl-2从5.0(标准差4.5)显著增加至9.1%(标准差6.7),p = 0.0004。单因素分析中,高剂量奥美拉唑使胃体部Ki-67表达增加更为显著:35.3%(标准差54.8),而常规剂量为-10.1%(标准差40.6),p = 0.022。多因素分析中,治疗前后胃体部Ki-67显著降低(p = 0.011),而高剂量奥美拉唑(p = 0.0265)、使用非甾体抗炎药(p = 0.0208)和吸烟(p = 0.0296)显著增加Ki-67表达。治疗后胃体部Bcl-2显著增加(p = 0.0003)。

结论

我们的研究结果表明,Bcl-2可能是消化性溃疡和消化性溃疡出血发病机制中的一个重要因素。此外,高剂量奥美拉唑增加了Ki-67的表达,这可能会促进消化性溃疡的愈合过程。

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