乳果糖对门静脉高压鼠肠道屏障功能的影响

Protective effects of lactulose on the intestinal tract barrier in rats with portal hypertension

目的:研究乳果糖对门静脉高压大鼠肠上皮细胞紧密连接蛋白的表达、细菌易位及内毒素血症的影响。方法:用50只雄性SD大鼠建立CCl4橄榄油复合法门静脉高压模型,并行影像学检验。造模后大鼠随机分为治疗组、对照组和单纯模型组。治疗组即乳果糖组,灌服乳果糖每次5mL/kg,每日2次,直至大鼠排稀便(共7d);对照组仅灌服相同浓度的葡萄糖水。8d后处死大鼠,取血、肝、脾、肾和肠系膜淋巴结组织匀浆后作细菌培养,测细菌易位率;取小肠组织行HE、Masson染色和超微病理的观察研究;测定血内毒素;用免疫组织化学方法测定小肠紧密连接蛋白表达水平。结果:与对照组及模型组比较,治疗组细菌易位发生率明显降低(P<0.05),其肝功能得到显著改善(P<0.01),血清内毒素水平(0.18±0.09)EU/mL亦有明显降低(P<0.01),紧密连接蛋白表达亦有显著差异(P<0.01)。结论:乳果糖灌胃可增加门静脉高压大鼠肠上皮细胞紧密连接蛋白的表达,维持肠上皮紧密连接,减少肠道细菌易位,减轻内毒素血症,并在一定程度上改善肝功能。为临床门静脉高压病人的治疗提供新的思路和理论基础。

Objective To investigate the effects of lactulose on the intestinal epithelial tight junction, bacterial translocation （BT） and intestinal endotoxemia in rats with portal hypertension. Methods Animal models of portal hypertention were established in 50 male Sprague-Dawley rats by subcutaneously injection of carbon tetrachloride （CCl4）. Then the rats were randomly divided into 3 groups： ① treatment group （T group）, received lactulose syrup （5 mL/kg） feeding twice daily for 7 days, ② control group（C group）, received glucose feeding only, and ③ portal hypertension group （M group） as the control group. After 8 days, all rats were sacrificed. Whole blood, liver, splenic, and kidney tissues, together with the mesenteric lymph nodes were collected for germ culture and bacterial translocation detection. The uhrastrueture of intestinal epithelial tight junction and the intestinal villi were observed by electron microscopy. The transmembrane binding protein （occludin） expression in the terminal ileum was detected by immunohistochemistry assay. The plasma endotoxin was also determined. Results The translocation of bacteria was found in groups M and C. Group T demonstrated improved liver function. The plasma endotoxin in group T was 0.18±0.09Eu/ml, which was significantly lower than that of groups C （0.35±0.07Eu/ml） and M （0.46±0.08Eu/ml, P〈0.01）. The oceludin expression was decreased in groups M and C than that in group T （P〈0.01）. Conclusions Lactulose lavage could induce occludin expression, maintain the intestinal epithelial tight junction, reduce the bacterial translocation and diminish the endoxemia. This study might provide a new rationale in the treatment of cirrhosis patients with portal hypertension.