内皮素-1对门静脉高压大鼠胃黏膜微循环的调节机制  

Regulation of gastric mucosal microcirculation by endothelin-1 during the development of rat portal hypertension gastropathy

作　　者：陈桂明[1] 周岩冰[2] 于红[3] 王东升[2] 陈春球[1] 尹路[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院消化外科研究所,上海200025 [2]青岛大学医学院附属医院普外科,青岛266012 [3]青岛大学基础医学院,青岛266021

出　　处：《外科理论与实践》2006年第3期201-204,共4页Journal of Surgery Concepts & Practice

摘　　要：目的:检测内皮素A受体(endothelin A receptor,ETA)mRNA在胃黏膜微循环血管上的表达位点,探讨内皮素-1(ET-1)对肝硬化门静脉高压大鼠胃黏膜微循环的调节机制。方法:用60%CCL4(0.3ml/100 g体重)皮下注射方法制作大鼠肝硬化门静脉高压性胃病模型。实验共分4组:正常对照组(n=13)、肝细胞变性坏死期组(n=20)、肝细胞结节状增生期组(n=20)和假小叶形成期组(n=18)。应用mRNA原位杂交技术确定ETA受体的表达部位,以能发现ET-1在胃黏膜微循环血管壁的作用位点,并测定实验大鼠门静脉压力、外周及门静脉血ET水平,以动态观察肝硬化门静脉高压形成过程中门静脉压力、门静脉与外周血ET水平变化及其规律。结果:Wistar大鼠在肝硬化门静脉高压形成过程中,其胃黏膜厚度增加,黏膜淤血;门静脉压力呈梯度性升高;外周及门静脉血浆ET水平随门静脉压力升高而降低;胃黏膜ETA mRNA主要在黏膜基底部的微循环前微动脉和后微静脉血管壁表达,其表达水平随ET浓度的降低和门静脉压力的升高而增加,且其在小动脉表达明显强于小静脉。结论:大鼠在肝硬化门静脉高压形成过程中,其外周及门静脉血浆ET水平呈进行性降低;胃黏膜微循环血管壁中的ETA mRNA表达量增加,呈现上调趋势;ET及其受体mRNA表达的这种变化可能与肝硬化门静脉高压大鼠胃黏膜微循环功能障碍有关。Objective To determine the expression of endothelin A receptor mRNA in gastric mucosal microcirculation, and to explore the mechanism involving endothelin-1 and its receptor during the development of liver cirrhosis and its accompanying portal hypertension gastropathy （PHG） in Wistar rats. Methods The rat liver cirrhosis and PHG model was established by subcutaneous injection of tetrachloride （CCL4）. Wistar rats were divided into 4 groups： ① control group （n=13）, ② degeneration and necrosis period group （n=20）, ③ nodule regeneration period group （n=20）, and ④ pseudo-lobule period group （n=18）. In situ hybridization of mRNA was used to detect the location and the quantity of endothelin-A receptor expression in the gastric mucosal microcirculation. The pressure and endothelin-1 level in both the portal vein and peripheral blood were determined, during the whole process of liver cirrhosis and PHG formation. Results Along with the formation of liver cirrhosis and PHG, the gastric mucosa became thicker and more congestive. The portal pressure elevated gradually, followed by the decrease of endothelin-1 levels in both the peripheral and the portal blood. ETA mRNA expression was significantly elevated in the postcapillary venule and the precapillary arteriole, and predominantly in the latter. Conclusions The endothelin levels in both the portal and peripheral blood decrease gradually with the formation of liver cirrhosis and portal hypertension in the rats. The ETA mRNA expression in the gastric mucosal microcireulation increases gradually with the descending of endothelin level. These changes seem to be related to the formation of portal hypertension gastropathy.

关 键 词：内皮缩血管肽类 微循环 高血压 门静脉 胃黏膜 大鼠 

分 类 号：R657.34[医药卫生—外科学]