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硫糖铝、西咪替丁和雷贝拉唑对乙醇-盐酸诱导的胃损伤愈合过程中黏膜羟脯氨酸含量的影响。

Effects of sucralfate, cimetidine and rabeprazole on mucosal hydroxyproline content in healing of ethanol-hcl-induced gastric lesions.

作者信息

Arisawa Tomiyasu, Shibata Tomoyuki, Kamiya Yoshio, Nagasaka Mitsuo, Nakamura Masakatsu, Fujita Hiroshi, Hasegawa Shin, Harata Masao, Nakamura Masahiko, Mizuno Tamaki, Tahara Tomomitsu, Ohta Yoshiji, Nakano Hiroshi

机构信息

Department of Gatroenterology, Fujita Health University, School of Medicine, Kutsukake-cho, Toyoake, Japan.

出版信息

Clin Exp Pharmacol Physiol. 2006 Jul;33(7):628-32. doi: 10.1111/j.1440-1681.2006.04418.x.

Abstract
  1. No general consensus has been reached on the treatment of acute gastric lesions. The aims of the present study were to clarify the effects of sucralfate, cimetidine and rabeprazole monotherapies and combination therapies on acute gastric lesions from the viewpoint of connective tissue regeneration. 2. Gastric lesions were experimentally created by the oral administration of 50% ethanol-0.15 mol/L HCl to rats. After 30 min, the anti-ulcer agents sucralfate (100 mg/kg), cimetidine (20 mg/kg) and rabeprazole (2 mg/kg) were administered separately or in combination and the stomach was excised at different times to measure the level of hydroxyproline in the gastric mucosa and determine lesion index. Immunostaining against prolylhydroxylase was performed on some specimens. 3. In the control group, lesion index decreased linearly from 30 min after ethanol-HCl administration and the level of mucosal hydroxyproline peaked between 2 and 4 h later. Although sucralfate significantly promoted lesion healing, it had no effect on mucosal hydroxyproline level. Cimetidine suppressed increases in mucosal hydroxyproline and prolonged lesion healing, but these findings were reversed by combining cimetidine and sucralfate. Rabeprazole had no significant effect on lesion healing, but promoted lesion healing in combination with sucralfate. Immunohistochemical analysis showed that prolylhydroxylase was expressed in spindle cells that lined the glandular cells in a boundary area between normal and injured tissues. 4. Under conditions in which the effects of intragastric pH are minimal, sucralfate is superior to antisecretory agents in promoting the healing of acute gastric lesions.
摘要
  1. 关于急性胃损伤的治疗尚未达成普遍共识。本研究的目的是从结缔组织再生的角度阐明硫糖铝、西咪替丁和雷贝拉唑单一疗法及联合疗法对急性胃损伤的影响。2. 通过给大鼠口服50%乙醇 - 0.15 mol/L盐酸来实验性地造成胃损伤。30分钟后,分别单独或联合给予抗溃疡药物硫糖铝(100 mg/kg)、西咪替丁(20 mg/kg)和雷贝拉唑(2 mg/kg),并在不同时间切除胃以测量胃黏膜中羟脯氨酸水平并确定损伤指数。对一些标本进行脯氨酰羟化酶的免疫染色。3. 在对照组中,损伤指数在乙醇 - 盐酸给药后30分钟开始线性下降,黏膜羟脯氨酸水平在2至4小时后达到峰值。虽然硫糖铝显著促进损伤愈合,但对黏膜羟脯氨酸水平无影响。西咪替丁抑制黏膜羟脯氨酸增加并延长损伤愈合时间,但西咪替丁与硫糖铝联合使用可逆转这些结果。雷贝拉唑对损伤愈合无显著影响,但与硫糖铝联合使用可促进损伤愈合。免疫组织化学分析表明,脯氨酰羟化酶在正常组织与损伤组织边界区域的腺细胞内衬的梭形细胞中表达。4. 在胃内pH影响最小的条件下,硫糖铝在促进急性胃损伤愈合方面优于抗分泌药物。

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