Expression And Effect Of Nnclear Factor-kappa B And Cyclooxygenase 2 In Animal Model Of Alcoholic Liver Injure

Objectives:This study establishes animal model of acute alcoholic liver injure by large amounts of alcohol in short term while giving intraperitoneal injection of NF-κB blocker PDTC, thus to explore NF-κB and the mechanism of cyclooxygenase-2 interaction mechanisms of acute alcoholic liver injure in rats intervened by PDTC and influence of PDTC on TNF-αMethodology:1. The intervention group after 12 hours of fasting and water per day, give them lavage twice per day for 14 days by 55%alcohol 8g/kg.d, intraperitoneal inject PDTC 30 minutes before each time of lavage from the third day on with the dosage of 50mg/kg.d a week. The model group alcohol lavage for the third day, intraperitoneal injection with the same amount of normal saline, and other operations are the same with PDTC intervention group. For control group, give lavage and intraperitoneal injection with the same amount of normal saline. Rats were sacrificed 12 hours later than last time of lavage and intraperitoneal injection on the first and second week,collect blood samples from the heart and separate the serum, get and fix hepatic tissues with formalin immediately after blood collecting, and For the pathological and immune to organize a chemical test.2. Automatic biochemical analyzer using the serum ALT and AST values, paraffin-embedded liver tissue, sliced to do HE staining and immunohistochemistry (SABC), observe the pathological changes in liver tissue and NF-κB, cyclooxygenase-2 expression and distribution.Results:1. Comparison on ALT and AST Value of Rats Serum: Comparing model group to control group and intervention group to model group on the first and second week of experiment, the ALT and AST values are obviously changed, have the statistical significance(P<0.01); and comparing the first and second week of model group, both of its serum ALT and AST value increased sharply have the statistical significance (P<0.01).2. Pathologic Examination: HE staining results:On the first and second week, comparing to the model group and control group, its hepatic cells began to swell, visible fat vacuoles of varying sizes, strong necrosis was noted in some lesions, inflammatory cell infiltration, with time in the model group increased. PDTC intervention group comparing to the model group of fat cells as liver and inflammatory cells is lighter.3. Results of Immunohistochemical Stains3.1 NF-κE,COX-2,TNF-a positive cells were mainly distributed around the central vein. In the model group, the expression of NF-κB,COX-2,TNF-a has the higher statistical significance than the control group on the first and second week, statistically significant (P<0.01); percentage of positive expression of intervention group lowered remarkably comparing to the model groups (P<0.05). percentage of positive expression of the model group was much higher in the second week than that of the first week, statistically significant (P<0.05)3.2 COX-2 and NF-κB expression in hepatic tissues show positive correlation (Spe-arman grade related r=0.435, P<0.05). 3.3 NF-κB and TNF-a expression in hepatic tissues show positive correlation (Spe-arman grade related r=0.336, P<0.05)3.4 COX-2 and TNF-a expression in hepatic tissues show positive correlation (Spe-arman grade related r=0.702, P<0.01).Conclusion:1) PDTC inhibited NF-κB activation and the reduced COX-2 and TNF-a expression2) NF-κB and COX-2 involved in acute alcoholic liver injury during development, and COX-2 expression may be mediated by the NF-kB.3) NF-κB and COX-2 played a role in acute alcoholic liver injury through the activation of TNF-a.