The Effects Of Dietary Factors On Acute Pancreatitis And Its Mechanisms

Acute pancreatitis (AP) is an acute abdomen illness. The incidence is about 5.4/10~5 in England and 79.8/10~5 in America. There is an increasing trend with AP in latest decades. Its damages not only occur in local pancreas but also involve in distant organs. Some studies showed that dietary factors are closely related to AP. Therefore, the study on prevention against AP with dietary measure and its mechanisms are in significance in both theory and practiceIn the present study, an epidemic study on the dietary factors of patient with AP was carried out to confirm the risk and to find out the protective factors. Then, an animal model of AP was established. In order to observe the effects of the dietary factors on the mice with AP, the mechanisms were studied in three, i.e. the oxidative stress the pancreas, the release of cytokines in the lung tissue and the failure of the microcirculation in the mesentery.The present study includes five parts as follows:1. A case-control study on the dietary factors for patients with acute pancreatitisObjective: To explore association between dietary factor and acute pancreatitis (AP), providing scientific evidences for the prevention of patient with AP. Methods: The subjects in case group were 100 AP patients hospitalized in the provincial hospital and above; the subjects in control group 1 were 100 patients hospitalized in the orthopaedics of the same hospital as cases, and the subjects in control group 2 were from communities. Controls were matched to cases for age(±2.5y) and sex. All of them were interviewed with uniform questionnaires. Conditional logistic regression was used for univariate and multivariate analysis. Results: The results indicate that AP was significantly associated with irregular eating (OR=3.1810), engorgement after hunger (OR=1.7239), high animal fat consumption (OR=1.4433), dink more alcohol once (OR=3.6348). High rice and flour consumption (OR=0.5391) , oftentimes eating greenstuffs (OR=0.3494), Oftentimes drink milk and yoghourt (OR=0.7584) were inversely associated with AP. Conclusion: The study suggests that dietary factors may play an important role in AP development <, Oftentimes eating animal fat, high oil consumption (more than 50g), high meat consumption after suffering two days (more than 250g), dink more alcohol once (ethanol more than 50g) and engorgement after hunger are risk factors. High Rice or flour consumption (more than 800g), Oftentimes eating greenstuffs and drinking milk are protective factors.2. Acute Necrotizing Pancreatitis induced by L-arginine in miceObjective-. The purpose of this study is to induce a simple and repeatable model of acute pancreatitis. Methods: AP was induced in male mice by injecting 200X2 mg/100 g-bw of L-arginine intraperitoneally in a 1-h interval, Control mice received the same quantity of 0.9% NaCl. Bloodsamples were taken from removing eyeballs for amylase activities analysis and pancreas were removed for pathologic observation at 0, 6, 12, 24, 48, 72h after the second injection. Result: Serum amylase activities significantly increased at 6, 12, 24h and peaked at 6h. While no significance was observed at 48h and 72h compared with the control group. Histopathological results revealed that the acinar architecture was partially destroyed with necrosis and interstitial edema and inflammatory infiltrate at 24h, necrosis and degeneration had markedly disrupted the acinar architecture at 48h. Conclusion: The present study demonstrated that two times of intraperitoneal injection with the big dosage of L-arginine can be induced a simple, repeatable, noninvasive experimented mouse model of acute necrotizing pancreatitis.3. Orthogonal trail about the effects of dietary factors at different levels on mice with APObjective: To determine levels of four dietary factors (that is greenstuffs A, lard B, laminaria C, alcohol D) treating mice with acute necrotizing pancreatitis induced by L-arginine in mice. Methods: Mice were fed on for three weeks according to L9 (34) orthogonal design. Then model of AP were induced by L-arginine. The numbers of survival animal and histopathological change were observed. Serum amyalse activities were analyzed. Data was used for variance analysis. Result: The primary and minor order and levels of the four diet factors affecting mice survival condition, histopathological score and serum amyalse activities are B2C1A2D1 ^ A2C2D2B3^ D2C2A2Bij respectively. Conclusion: Levels of all the four dietary factors suitable for the present study are the second ones, i.e. 2.5% laminaria, 5% greenstuff, 10% lard and 20% ethanal.4. The effects of four dietary factors on mice with AP induced by L-arginine and oxidative stress mechanism in pancreas tissueObjective: To explore the effects of the four dietary factors on mice with AP induced by L-arginine and oxidative stress mechanism in pancreas tissue. Method: One hundred and eighty mice were divided into six groups, i.e. control group, AP group, laminaria group, greenstuffs group, lard group and alcohol group. Mice in four treatment groups were fed with the diet containing 2.5% laminaria, 5% greenstuff, 10% lard, regular diet respectively. The mice in alcohol group were perfused with 20% alcohol for 3 days before injecting L-arginine. The model of AP was established by the injection of L-arginine, The blood samples and pancreas were obtained at 12th h after the second injection. Serum amyalse, pancreas malondialdchehyche (MDA) content, superoxide dismutase (SOD) and nitric oxide (NO) were measured by colorimetry. Result: Compared with control group, mortaltity rate (32%) was higher, pancreas MDA and NO increased significantly, while pancreas SOD decreased significantly in AP model group. However, mortaltity rate (26%) was lower, histopathological score, MDA, NO levels of mice in greenstuffs group were significantly decreased, SOD was significantly higher than those in AP group. Mortaltity rate (46.15%), histopathological score, MDA, NO levels of mice in lard group were higher, moreover. SOD was lower than those in AP group. In laminaria group, MDA and NO decreased while SOD increased, but no significant difference was observed. In alcohol group mortaltity rate (33.33%) and histopathological score ascend. But SOD, MDA, NO levels are similar to those of AP group. Conclusion: The results indicateL-arginine. Greenstuffs may reduce oxidative damage of pancreas and lard may be an important factors in pancreatic injury of mice with AP induced by L-arginine, The mechanisms of laminaria and alcohol causing pancreatic damages have not been defined and need to further study.5. The effects of four dietary factors on lung tissue cytokines and mesenteric microcirculationObjective: This study was aimed at an assessment the effects four dietary factor on lung tissue cytokines and mesenteric microcirculation failure. Methods: The methods of mice feeding and grouping were the same as the fourth part. Tumor necrosis factor-alpha (TNF- a ) was determined by radioimmunoassay. Intercellular adhesion molecule-1 (ICAM-1) was localized by light microscopic immunohistochemistry and light density by computerized image analysis. Mesenteric microcirculation was observed by intravital fluorescence microscopy of erythrocytes labeled by FITC (FITC-RBC) in dark and bright light. Results: In the Apgroup, compared with the control group, content of TNF- a and ICAM-1 expression in lung tissue significantly increased, while microvessel diameter, number of capillary net, number of functional capillary, velocities and flow capacity of FITC-RBC, were all decreased significantly. In the greenstuffs group, compared with the AP model group, content of TNF- a and ICAM-1 expression in lung tissue decreased significantly, microvessel diameter, number of capillary net, number of functional capillary, velocities and flow capacity of FITC-RBC were all significantly increased. In the lard group compared with the AP model group, ICAM-1 expression in lung tissue increased significantly, velocities and flow capacity of FITC-RBC decreased, but not significant. In the laminaria group, compared with APwith AP model group, velocities and flow capacity of FITC-RBC were increased significantly. Conclusion: The results indicate that TNF- a and ICAM-1 play important roles pancreatitis-associated lung injury, mesenteric microcirculation failure occurred in the AP mice. The diet with 5% greenstuffs can improve the mesenteric microcirculation effectively. The diet with 10% lard can aggravate lung damage and the failure of mesenteric microcirculation. ICAM-1 increase may contribute to lung damages of mice in lard group induced by L-arginine.In general, greenstuffs play a protective role in mice with AP in mechanism involved in reversing oxidative stress, modifying cytokines level, ameliorating mesenteric microcirculation. Whereas lard aggravated pathological injures in mice with AP. Laminaria has a alleviate trend in oxidative stress in the pancreas. Alcohol causing pancreatic damages are not significant and should be further studied.