Effect Of Glutamine On Intestinal Mucosal Barrier After Occlusion Of Portal Vein In Rats With Obstructive Jaundice

【Background】Obstructive jaundice(OJ) is a common symptom of the carcinoma of the pancreas and biliary tract, and surgical resection is still the mainly effective means. However intestinal mucosal barrier dysfunction caused by obstructive jaundice, leading the bacterial and endotoxin translocation and multiple organ damage, will increase the incidence of postoperative complications. During the operation, portal vein occlusion(PVO) has to be performed, but portal venous system congestion caused by PVO can cause intestinal mucosa ischemia and ischemia/reperfusion injury. So under this pathophysiological condition, how to protect the intestinal mucosal barrier, reduce endotoxin translocation and decrease the incidence of postoperative complications is worthy of study. Many studies has found that glutamine(Gln) can promote enterocytes growing and differentiation, prevent intestinal mucosa atrophy, have a protective effect on the intestinal mucosal barrier. There were few reports about the feature and mechanism of glutamine on intestinal mucosal barrier after occlusion of portal vein in rats with obstructive jaundice.【Objective】The aims of this study were to establish the model of obstruction jaundice and portal vein occlusion in rats, to study the effect and the feature of portal vein occlusion on intestinal mucosal barrier in rats with obstructive jaundice and investigate the protective effect of glutamine on intestinal mucosal barrier after portal vein occlusion in rats with obstructive jaundice, and it would provide theoretical basis for clinical treatment.【Methods】Fifty male Wistar rats were randomly divided into five groups: control group (control),sham-operation group(sham),obstructive jaundice group(OJ),obstructive jaundice + portal vein occlusion group(OJ+PVO) and Gln group(Gln). In group OJ,OJ+PVO and Gln, the common bile duct(CBD) was ligated to establish the animal model. Seven days later the portal vein was occluded 30min in group OJ+PVO and Gln. The rats of group Gln were fed glutamine for 7 days. Sham group had the bile duct mobilized but not tied, while group OJ just had the CBD ligated but not occluded the portal vein. Then the samples of all rats were collected on the 7th day, the following items were detected: the level of portal vein blood endotoxin,D-lactate, pathologic morphology change of intestinal mucosa. And immunohistochemistry was used to examine the distribution and expression of tight junction proteins (ZO-1). Data were analyzed chi-square test and student's test, p<0.05 was considered statistically significant.【Results】1,Intestine mucosal villi integrity existed in control and sham group rats. Significant short,loose,deletion of intestinal mucosal villi were observed in OJ+PVO rats compared with OJ rats, and oral administration of Gln prevented the above findings. And there was a significant deduction in total mucosal thickness in group OJ+PVO [452.4±42.6μm(OJ+PVO) vs. 498.7±50.8μm(OJ) vs. 478.8±38.7μm(Gln)] and villous height [277.2±35.1μm(OJ+PVO) vs.319.9±33.2μm(OJ) vs. 299.9±30.0μm(Gln)]in jaundiced animals.2,Structural and ultrastructural abnormalities were more evident in the mucosa of the terminal ileum of group OJ+PVO rats than that of group OJ rats under the TEM. Electron microscopy revealed oedematous change associated with mild inflammation, disruption of desmosomes, and the formation of lateral spaces between enterocytes. In addition, enterocytes showed cytoplasm vacuolation and mitochondrial swelling.3,There was a significant increase in portal vein endotoxin in group OJ+PVO [3.23±0.50EU/mL(OJ+PVO) vs. 1.93±0.34EU/mL(OJ)], p<0.05. The portal vein endotoxin level(2.01±0.32EU/mL) in group Gln was significantly lower than OJ + PVO group, p<0.05.4,There was a significant increase in portal vein D-lactate in group OJ+PVO [6.96±0.89mg/L(OJ+PVO) vs. 4.53±0.71mg/L (OJ)], p<0.05. The portal vein D-lactate level(3.50±0.41mg/L) in group Gln was significantly lower than OJ + PVO group, p<0.05.5,In control and sham groups, the staining of ZO-1 displayed a continuous and uniform distribution along the under surface of the villae. In OJ group, ZO-1 staining appeared discontinuous and vague, with rough edges and spiculate processes, while ZO-1 staining decreased more significantly in OJ+PVO group than that in OJ group. Compared with group OJ+PVO, in group Gln the distribution of ZO-1 recovered in some extent and the strong positive express ratio elevated significantly(P<0.05).【Conclusions】1,The study showed that PVO could increase the damage of intestinal mucosal barrier under the pathophysiological condition of OJ, resulting in increasing intestinal permeability, bacterial and endotoxin translocation.2,Glutamine had a protective effect on the intestinal mucosal barrier, could alleviate the damage of the intestinal mucosal barrier after the portal vein occlusion under the obstructive jaundice condition, decrease the intestinal mucosal permeability and reduce the bacteria and endotoxin translocation.