大鼠门脉高压性胃病形成中胃黏膜诱导型一氧化氮合酶的表达及氨基胍的干预作用  

Expression of inducible nitric oxide synthase in gastric mucosa in the development of portal hypertensive gastropathy in rats and the interventional effect of aminoguanidine

作　　者：王凝[1] 展玉涛[1] 史小林[3] 高福生[1] 谢新纪[2] 刘宾[1] 

机构地区：[1]首都医科大学附属北京同仁医院消化内科,100730 [2]首都医科大学附属北京同仁医院病理科,100730 [3]首都医科大学生殖医学中心,100730

出　　处：《中华临床营养杂志》2009年第4期220-223,I0002,共5页Chinese Journal of Clinical Nutrition

摘　　要：目的探讨大鼠胃黏膜诱导型一氧化氮合酶（iNOS）在门脉高压性胃病形成中的作用，以及氨基胍（AG）的干预作用和机制。方法将54只SD大鼠随机分为对照组（n=14）、模型组（n=20）和AG组（m=20）。模型组予每周2次皮下注射40％CCl4橄榄油溶液3ml／kg，AG组与模型组做相同处理的同时予AG50mg·kg^-1·d^-1饮用，对照组予每周2次皮下注射橄榄油3ml／kg。每组再根据制模时间分别分为6周组及12周组，共计6组。分别观察各组大鼠胃黏膜病变情况，测定胃黏膜溃疡指数及门静脉压力，应用免疫组化SABC法检测胃黏膜iNOS的表达。结果模型组大鼠胃黏膜溃疡指数均明显高于相应对照组（P均〈0．01），AG6周及12周组胃黏膜溃疡指数则明显低于模型组（P〈0．05；P〈0．01）。模型6周及12周组门静脉压力均较相应对照组升高（P〈0．05；P〈0．01），AG6周及12周组门脉压力均较相应模型组降低（P〈0．05；P〈0．01）。模型各组胃黏膜iNOS表达均较相应对照组明显升高（P〈0．01），AG各组均较相应模型组水平明显下降（P〈0．01）。结论门脉高压性胃病形成中的不同阶段均出现胃黏膜iNOS高表达，且逐步加重，iNOS在门脉高压性胃病形成中可能起重要作用；AG可明显减轻门脉高压性胃黏膜病变程度，其机制可能主要通过抑制胃黏膜iNOS表达。Objective To study the expression and role of inducible nitric oxide synthase （iNOS） in gastric mucosa in the pathogenesis of portal hypertensive gastropathy （PHG） in rats, and to investigate the interventional effect of aminoguanidine （ AG）, a selective inhibitor of iNOS. Methods Fifty-four male SD rats were randomly divided into control group （ n = 14）, model group （ n = 20）, and AG group （ n =20）. The model group was induced by 40% CCl4-ohve oil solution （3 ml/kg, twice a week） subcutaneously, and the AG group was treated by drinking 50 mg·kg^-1· d^-1 AG in addition to the injection of CCl4. Half of these rats were sacrificed at the end of Week 6 and Week 12, respectively. The morphological and histological changes in gastric mucosa were evaluated. The ulcer index （UI） of gastric mucosa and portal venous pressure were measured. The expression of iNOS in gastric mucosa was detected by immunohistochemical methods. Results The extent of histological changes and the UI of gastric mucosa in model group were more severe/higher than those in control group （ P 〈 0.01 ）, while the UI of gastric mucosa in AG group were significantly lower than that in model group （ P 〈 0.05 ; P 〈 0. 01 ）. The portal pressure in model group was significantly higher than that in control group （P 〈0.05 ） and was significantly higher than that in AG group （ P 〈 0.05 ）. The expression of iNOS in gastric mucosa in model group was significantly higher than that in control group （P 〈 0. 01 ） and was significantly higher than that in AG group （P 〈 0. 01 ）. Conclusions The expression of iNOS in gastric musosa remarkably increases with the development of cirrhosis, which may play an important role in the development of PHG. AG may remarkably ameliorate the degree of PHG, mainly by inhibiting the expression of iNOS in gastric musosa.

关 键 词：肝硬化 门脉高压性胃病 诱导型一氧化氮合酶 氨基胍 

分 类 号：R575[医药卫生—消化系统] R573[医药卫生—内科学]