The Study Of Protective Effect And Mechanisms Of Meloxicam On Intestinal Mucosal Barrier Injury Of Rats Withsevere Acuet Pancreatitis

The study of protective effect and mechanisms of Meloxicam onintestinal mucosal barrier injury of rats withsevere acuet Abstract:Objective:The aim of this study is to demontrate pancreatitis the protective effect of Meloxicam on intestinal mucosal barrier in rats with SAP and its possible mechamisms. Method:54 female Sprague-Dawley rats with the weight of 200-240g, were randomly divided into sham operation group (N group), severe acute pancreatitis group (P group), Meloxicam treatment group(M group).5% sodium taurocholate was retrograde injected into the pancreatic duct of the rats in P group and M group to induce SAP. Rats in N group whose pancreas were just flipped and striked gently with nothing injected. After operation, rats were deprived of food with free access to water. Rats in M group were injected with Meloxicam 2.5 mg/kg from Intraperitoneal injection respective after postoperative 1 and 24 hours, and the same dosage of 0.9% NS was injected in P group.6 rats of every group were humanely killed at 12,24,48 hours, pancreatic and 2 cm long ileal tissues that distant from ileocecal about 3 cm were taken for histopathologic examination. Blood was collected from inferior vena cava for detecting serum amylase, serocym serum endotoxin, serum tumor necrosis factor-a, serum interleukin-6, serum interleukin-10 and collected pancreas and mesenteric lymph node decting bacterial translocaton were determined at 12,24 and 48 hours after operation. All the results were analysed by Anova with SPSS 17.0.Result:1. Pathological change of pancreatic tissues:In general morphous, pancreas of N group were normal. With time continuing, the pancreatic tissues of P group were darken. Ascites, necrosis, hemorrhage and conglutination of pancreas and surrounding tissues were gradually serious. These also appeared in M group, but were better. Observation through light microscope:In N group, the structure of pancreatic tissues was integrity, there was no inflammatory cell. Disappearance of parts of lobular structure, edema, hemorrhage and necrosis of pancreatic tissues, and infiltration of inflammatory cells were obvious in P group, they were aggravated with time going. Changes of pancreatic tissues in M group at 12,24,48 hours were better than that in P group.2. Pathological change of small intestines tissues and pathological score:In general morphous, small intestine of N group were normal. With time going, the small intestines were expansion and darken in P group. Small intestines of M group turned better than that in P group. Observation through light microscope:There was no obvious abnormity in ileum tissues of N group. Edema of ileum lamina propria, necrosis of Columnar epithelial cells. Edema and thickening, highly reduced, disorganized of villous, Some villous become fracture and infiltration of inflammatory cells were aggravated in P group. The changes also turned better in M group. Pathological score:At 12 hours of N group, P group, M group, the scores were 0.67±0.52,5.17±0.75 and 4.67±0.82 respectively, P group was higher than N group (P<0.05), P group and M group had no obvious differences (P>0.05). At 24 hours of N group, P group, M group, the scores were 0.83±0.41,9.50±1.05 and 7.83±0.75 respectively, P group was higher than N group (P<0.05), M group was lower than P group (P<0.05). At 48 hours of N group, P group, M group, the scores were 1.00±0.63,12.00±0.89 and 9.33±0.82 respectively, P group was also higher than N group (P<0.05), M group was also lower than P group (P<0.05).3. AMY (U/L):The concentrations of AMY in the serum were increased, they were highest at 48 hours. At 12 hours of N group, P group, M group, the concentrations of AMY were 1048.51±78.34,4336.24±247.10 and 3196.25±194.55, respectively, P group was higher than N group (P <0.05), M group was lower than P group (P<0.05). At 24 hours of SO group, S group, M group, the concentrations were 1107.00±97.76, 8304.34±360.38 and 6174.25±261.69 respectively, P group was higher than N group (P<0.05), P group was lower than M group (P<0.05). At 48 hours of N group, P group, M group, the concentration were 1137.93±111.69,12142.49±1000.6 and 9168.20±195.30 respectively, P group was also higher than N group (P<0.05), M group was also lower than P group (P<0.05).4. TNF-a(pg/ml):At 12 hours of N group, P group, M group, the concentrations of TNF-a were 22.52±2.14 53.00±4.93 and 40.50±4.77 respectively, P group was higher than N group(P<0.05), M group was lower than P group(P<0.05). At 24 hours of N group, P group, M group, the concentrations were 22.10±3.04, 82.49±4.84 and 66.74±3.02 respectively, P group was higher than N group(P<0.05), M group was lower than P group(P<0.05). At 48 hours of N group, P group, M group, the concentrations were 24.23±2.74, 104.67±7.19 and 89.26±5.06, respectively, P group was higher than N group(P<0.05), M group was lower than P group (P<0.05).5. IL-6 (pg/ml):At 12 hours of N group, P group, M group, the concentrations of IL-6 were 43.76±2.89,104.52±7.46 and75.48±6.15 respectively, P group was higher than N group (P<0.05), M group was lower than P group(P<0.05). At 24 hours of N group, P group, M group, the concentrations were 45.48±3.88,138.86±7.07 and 118.49±8.11 respectively, P group was higher than N group (P<0.05), M group was lower than P group (P<0.05). At 48 hours of N group, P group, M group, the concentrations were 47.15±3.91,161.37±8.04 and 140.46±8.0 respective, P group was higher than N group(P<0.05), M group was lower than P group (P<0.05).6. IL-10(pg/ml):At 12 hours of N group, P group, M group, the concentrations of IL-10 were 33.75±6.98,55.85±6.34 and 101.89±10.93 respectively, P group was higher than N group (P<0.05), P group was lower than M group(P <0.05). At 24 hours of N group, P group, M group, the concentrations were 36.15±6.40,95.52±7.61 and 181.29±12.35 respectively, P group was higher than N group (P<0.05), P group was lower than M group (P<0.05). At 48 hours of N group, P group, M group, the concentrations were 35.91±7.26,84.22±11.98 and 181.29±12.35 respectively, P group was higher than N group (P<0.05), P group was lower than M group (P<0.05).7. ET (EU/ml):At 12 hours of N group, P group, M group, the concentrations of ET were 0.116±0.003, 0.628±0.042 and0.563±0.038 respectively, P group was higher than N group(P<0.05), M group was lower than P group (P<0.05). At 24 hours of N group, P group, M group, the concentrations were 0.116±0.003,0.628±0.042 and 0.563±0.038 respectively, P group was higher than N group (P<0.05), M group was lower than P group (P<0.05). At 48 hours of N group, P group, M group, the concentrations were 0.118±0.003,0.779±0.034 and 0.639±0.075 respectively, P group was higher than N group (P<0.05), M group was lower than P group (P<0.05).8. Bacterial culture results (culture positive rate (%)) and translocation rates:At 12 hours of N group, P group, M group, the rate were 5.6%,5.6% and 5.6% respectively, P group was higher than N group (P<0.05), M group was lower than P group (P<0.05). At 24 hours of N group, P group, M group, the rate were 22.2%,83.3% and 100% respectively, P group was higher than N group (P<0.05), M group was lower than P group (P<0.05). At 48hours of N group, P group, M group, the rate were 11.1%,50% and 16.7% respectively, P group was higher than N group (P<0.05), M group was lower than P group (P<0.05). Conclusion:The function of intestinal mucosal barrier damaged in the early phases of SAP. The Meloxicam through Selective COX-2 inhibitor (Meloxicam) selctivety inhibit COX-2 express in SAP and rectifying both the level of pro- and anti-inflammatory cytokines. Meloxicam Can significantly improve the permeability of intestinal mucosa and reduce the injury of intestinal mucosa barrier...