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Experimental Study On Protective Effect Of Cyclooxygenase-2 (COX-2) Inhibitor On Acute Pancreatitis And Secondary Of The Systemic Inflammatory Response In Rat

Posted on:2006-12-24Degree:MasterType:Thesis
Country:ChinaCandidate:N XuFull Text:PDF
GTID:2144360155473580Subject:Surgery
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BACKGROUND AND OBJECTIVE: The acute pancreatitis which own the character of calamitous pathogenetic condition and high opportunity of morbidity and mortality is a commonly acute abdomen in surgery. Except for impairment of pancreatic enzyme's autodigestion, many inflammatory mediators also participate and develop the natural course of pancreatitis. And at the same time the extent of impairment in extrapancreas organs are become more and more severity. Because of dysimmunity through the course of pancreatitis, the multiple organ dysfunction syndrome is apt to take place. The measurement which modulating pro- and anti-inflammatory cytokines, ameliorating the state of body's immunity and keeping immunologic balance in a lower level is benefit to control inflammation and elevate on prognosis in patients. As previous rat experiment, the inflammatory cytokines such as TNF- α , IL-6, IL-10, TGF- β and so on in serum of early phase of acute pancreatitis increased predominantly. After treated with COX-2 inhibitor, thepro-inflammatory cytokines such as TNF- a , IL-6 significantly decreased. Obvious improvement of index of the severity of the acute pancreatitis, including the blood routine counting, amylase and the secondary injury in lung tissue, also were observed after treatment with COX-2 inhibitor. So the purpose to cure the acute pancreatitis by COX-2 inhibitor can be achieved through inhibiting early enzyme namely cyclooxygenase-2 in the course of inflammation, decreasing products of arachidonic acid and blocking some relative component element through inflammatory cascade reactions. We don't know whether COX-2 inhibitor can also decrease the level of anti-inflammatory cytokines and rectify the abnormal immunity. According to this question, the objective of this experiment is to observe the effect of COX-2 inhibitor on prognosis of Sprague-Dawley (SD) rat and to discuss the probable mechanism of treatment in acute pancreatitis using by COX-2 inhibitor through establishing acute pancreatitis model and selecting two categories of COX-2 inhibitor (Mobic and Celecoxib) as interventional measurements.METHODS: First, thirty six female 6—7 weeks old SD rats were randomly divided into 4 groups: Group 1. The sham rats as a control ; Group 2. Acute pancreatitis model were established by retrograde pancreatic duct injection with 3.3% Sodium taurocholate at the volume of 2ml/kg weight ; Group 3. Six and two hours before operation, the rats were injected with Mobic 0.5ml from lavage-needlepoint respectively, and after it the model were established in the same way like group 2 ; Group 4. Six and two hours before operation, the rats were injected with Celecoxib 0.5ml from lavage-needlepoint respectively, and after it the model were established like group 2. Whenoperation were completed, the whole rats were all injected subcutaneously with 0.9% NaCl 2.5ml in both inguinal grooves. Second, the rats in four groups were killed at 2, 6, 24 hours after operation. The ordinary situation and the ascites rate were observed. The volume of ascites were collected and measured. Blood samples were taken for measurement of blood routine counting, blood amylase, IL-6 and IL-10. The tissue of pancreas were incised yet the wet weights and pathologic examination were also tested. RESULTS: 1. Twenty four hours after pancreatitis were induced, the volume of ascites, the wet weights of pancreas, the leukocyte counting, the blood amylase, the level of IL-6 and IL-10 in group 2 were (3.67±0.75) ml, (0.45±0.08) g, (16.07±1.17)xl09-U1, (5600.00±753.76) IU-L"1, (638.82±49.90) pg-ml"1 and (596.53±217.88) pg-ml"1 respectively. The same index in group 3 were (0.27±0.15) ml, (0.33±0.12) g, (6.77±3.21)xl09-L"\ (2610.00±492.20) IU-L"1, (293.06±71.00) pg-ml"1 and (229.87±17.60) pg-ml"1 respectively. The same index in group 4 were (0.63±0.49) ml, (0.33±0.05) g, (6.90±1.35)xl09-L'\ (2218.00±504.45) IU-L"1, (306.15±245.21) pg-ml"1 and (238.16±28.92) pg-mi"1 respectively. 2. Compared index in group 3 and group 4 to which in group 2 pre- and post-operation, every index improved significantly (P<0.05) except the wet weights of pancreas in 24 hours phase in this experiment.CONCLUSIONS: 1. Acute pancreatitis model established by retrograde pancreatic duct injecting with 3.3% Sodium taurocholate at the volume of 2ml/kg weight have a virtue of simple manipulation, easily controlled experimental condition, steady experiment result and good repetition. It's a suitable model for observation the therapeutic effect of various interferentialmeasurement on acute pancreatitis and secondary of the systemic inflammatory response in rat. 2. Cyclooxygenase-2 inhibitor can blockage the product of arachidonic acid, relieve the degree of inflammation reaction in pancreas and ameliorate the prognosis in pancreatic rat. It's protective effect may be achieved through rectifying both the level of pro- and anti-inflammatory cytokines and keeping immunologic balance in a lower level.
Keywords/Search Tags:cyclooxygenase-2 inhibitor, mobic, celecoxib, acute pancreatitis, Sodium taurocholate, systemic inflammatory response syndrome, animal model
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