The Protective Effect Of Curcumin On Intestinal Mucosal Barrier Of Rats With Obstructive Jaundice

Objective:Obstructive jaundice can lead to intestinal barrier dysfunction, severe infection, multiple organ dysfunction syndrome, and other complications. Many of the pathological states in obstructive jaundice depend on the disorders of intestinal barrier function. Bowel function is one of the most important factor to determine the prognosis of patients, it is directly related to operative mortality and the complications of patients. Cytokines and inflammatory mediators are the important factors that lead to injury of intestinal mucosal barrier. NF-κB as an important transcription regulators, early proinflammatory gene, plays an important role on the occurrence, development and regulation of inflammatory response when subjected to obstructive jaundice. Curcumin has anti-inflammatory, antioxidant and other biological effects. Studies have shown that curcumin can inhibit activation of NF-κB, it is non-specific inhibitors of NF-κB. In this study, by observing the effect of curcumin on intestinal tissue morphology and the effects of inflammatory cytokines, explore the protective effect and its possible mechanism of curcumin on intestinal mucosal barrier of rats with obstructive jaundice. Method:1 Animal model: Healthy male Sprague-Dawley rats were anesthetized by intraperitoneal injection with 10% chloral hydrate (0.3 g/kg).Then made a 3 cm incision in the middle of the abdomen, porta hepatis was exposed. Common bile duct was separated, and ligated with double No. 3-0 silk. Then cut at two ligation lines, and sutured abdominal wall. Common bile duct was only isolated in sham operation group, but not ligated.2 Animal groups: All Sprague-Dawley rats (n=30) were divided into three groups at random: sham operation group (n=10), obstructive jaundice group (n=10), and obstructive jaundice + curcumin group (n=10). The rats of SO group and OJ group were feed normally, curcumin was administered to rats 100 mg/kg?d in OJ+Cur group by gastric irrigation for 14 days since making the animal models.3 By light microscope observed pathological changes of rat intestinal tissue, and applied Image pro plus system to measure intestinal mucosal height and thickness.4 Assay endotoxin levels of plasma in endpoint chromo- genic TAL method.5 Using immunohistochemical method assayed expres- sion of NF-κB and ICAM-1 of intestinal mucosa.6 Assay serum TNF-α, IL-6 levels in radioimmunoassay method.7 Using spectrophotometry method assay activity of diamine oxidase of intestinal tissue. Results:1 The general states of ratsAfter ligating bile duct 48 h urine color turned yellow in rats, the fourth to fifth day fur of body turned yellow, and food intake was gradually reduced. After operation one week and two weeks, we had observed cystic dilatation of common bile duct near liver side in rats with obstructive jaundice, diffuse swelling of liver which was brownish-yellow.2 Ileal mucosa histopathological examinationIt was seen pigmentation of dark brown by naked eyes in small intestinal mucosa of rats with obstructive jaundice. Observed under light microscope, villus of intestinal mucosa neatly arranged, highly consistent, complete mucosal and villus in the SO group; villus of intestinal mucosa with disordere, sparse, fracture, edema, intestinal mucosal with atrophy, part of epithelial cell with necrosis, off, and inflammatory cell infiltration in the OJ group; compared with the SO group, height and thickness of ileal mucosa of rats in the OJ group, become smaller, thinner, the difference had statistical significance (P<0.01). Lesion of intestinal mucosal in the OJ+Cur group was significantly reduced than the OJ group, villus of intestinal mucosa neatly arranged, intestinal mucosal thickened, mild villous edema, no obvious epithelial cell loss, inflammatory cell infiltration reduced; after application of curcumin the height and thickness of intestinal mucosa obviously improved, compared with the OJ group the difference had statistical significance (P<0.05). the difference between the OJ+Cur group and the SO group had statistical significance (P<0.01).3 The plasma levels of endotoxinConcentration of endotoxin of plasma in the OJ group was significantly higher than that of the SO group, and there was significantly difference between two groups (P<0.01); Concentration of endotoxin in OJ+Cur Group was significantly decreased than that of the OJ group and SO group, the difference had statistical significance (P<0.01).4 The content of serum TNF-αand IL-6The concentrations of serum TNF-αand IL-6 in OJ group were significantly higher than that of the SO group, the difference had statistical significance (P<0.01); the concentrations of TNF-αand IL-6 in OJ+Cur group were significantly decreased than that of the OJ group and SO group, the difference had statistical significance (P<0.05).5 Activity of diamine oxidase of intestinal tissueThe activity of diamine oxidase of intestinal tissue in the OJ group was significantly lower than that of the SO group, the integrity and function of intestinal mucosa was damaged, the difference had statistical significance (P<0.01); in the OJ+Cur group it was significantly higher than that of the OJ group, the difference had statistical significance (P<0.05); the difference between the OJ+Cur group and the SO group had statistical significance (P<0.01).6 Expression of NF-κB in the intestinal tissue NF-κB-positive cells was rare in the SO group, but in the OJ group, ther were a large number of the cytoplasm and nucleus of intestinal epithelial cells and inflammatory cells expressing NF-κB, the difference had statistical significance (P<0.01); the expression of NF-κB in the OJ+Cur group was significantly lower than that of OJ group (P<0.05); the difference between the OJ+Cur group and the SO group had no statistical significance (P>0.05).7 Expression of ICAM-1 in the intestinal tissueICAM-1 was mainly expressed in cytoplasm of glandular cells and inflammatory cells, brown cytoplasm was positive expression; in the OJ group significantly higher expression than that of SO group (P<0.01), after administer of curcumin, expression of ICAM-1 decreased significantly (P<0.05); the difference between the OJ+Cur group and the SO group also had statistical significance (P<0.05).Conclusions:1 Intestinal mucosa of rats with obstructive jaundice exist a certain degree of injury.2 When subjected to obstructive jaundice, the expression of NF-κB increases the expression of TNF-α, IL-6, ICAM-1, resulting in injury intestinal mucosal barrier.3 Curcumin may be through inhibiting expression of NF-κB and TNF-αto reduce the expression of TNF-α, IL-6, ICAM-1 and protect intestinal mucosal barrier injury of obstructive jaundice.