The pathogenesis of acute pancreatitis(AP)has been a hot issue around the world.Regarding the pathogenesis of AP,there are mainly the trypsin autodigest doctrine,microcirculation theory,inflammation and cell-medium theory,theory of intracellular calcium overload,bacterial translocation and the "two-hit" theory,oxidative stress and doctrine of NO role,and so on.Resveratrol,a natural plant extraction with a wide therapeutic effect of anti-inflammation and anti-oxidation,inhibits platelet aggregation,improves microcirculation and has other pharmacological effects.In recent years,we have carried out extensive and in-depth literature-based studies on the mechanisms for AP and the therapeutic effect of resveratrol on rat AP models,and confirmed that resveratrol could relieve AP-caused damage to the pancreas and the resulting multiple-organ injury.

Objective To establish a stable brain injury model with pancreatitis and explore the mechanism of brain injury resulting from severe acute pancreatitis (SAP) in experimental rat models. Methods Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups: sham operation (SO) group, SAP group and trypsin group, with eight rats in each. Brain tissue and pancreas tissue specimens were collected at 12 h after treatment. Death rate in each group was evaluated; the level of tight junction protein zonula occludens 1 (Zo-1) was determined by enzyme-linked immunosorbent assay. The ultrastructure of the brain tissues was examined using transmission electronic microscope; pathological changes in the brain tissues were observed with HE staining. Results The death rate was increased significantly in SAP group compared with that in trypsin group; no rats in SO group died. Zo-1 level was obviously lower in SO group than in SAP group and trypsin group (P<0.05). The ultrastructural changes were seen in the latter two groups, including obvious neuronal cell swelling, capiliary stasis, increased vascular permeability, thrombosis and cell apoptosis. Conclusion Trypsin may cause brain injury with pancratitis. The death rate of SAP model established by trypsin was low. We have provided a stable animal brain injury model for further study and treatment of brain injury.

Objective To investigate the effects of resvertrol on apoptosis and the expression of apoptosis-regulated genes Bax in rats with experimental severe acute pancreatisis.Methods Totally 54 SD rats were randomly divided into 3 groups: sham-operation group(SO),severe acute pancreatitis group(SAP),and resveratrol-treated group(RES).In SO group the pancreases were slightly flipped only.The SAP model was set up by giving 40g/L sodium chrolate(1mL/kg) through pancreatic duct,and resveratrol(5mg/mL,10mg/kg) was given intravenously.Apoptosis of mucosal cells was detected by TUNEL methods,and the expression of Bax protein was determined by SP immunohistochemical technique.Results The apoptotic index of mucosal cells in SAP group at 3,6 and 12 hours after induction of severe acute pancreatitis was significantly higher than that in resveratrol-treated group((P

?-adrenoceptor,whose subtypes ?1-and ?2-adrenoceptor are expressed on panreatic cancer cells,is closely related to the occurrence and development of pancreatic cancer.?-adrenoceptor agonists epirenamine,isopropylarterenol and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK) induce pancreatic cancer proliferation.Research on the molecular mechanism is as follows: Activating ?-receptor can stimulate protein kinase A(PKA)/arachidonic acid(AA) pathway in pancreatic cancer cells.NNK also stimulates mutation of Ras and the activation of Src tyrosine kinase and Ras,followed by activation of mitogen activated protein kinase(MAPK) pathway.?-adrenoceptor can make the epidermal growth factor(EGFR) pathway transactivated,and the EGFR and ?-adrenergic signalling pathways might synergize to activate Src and Ras.Increased evidence suggests that patients with pancreatic adenocarcinoma share many risk factors,such as smoking and chronic depression,with cardiovascular disease patients.Drugs to block ?-adrenoceptor in cardiovascular diseases might be used for the prevention and treatment of pancreatic cancer.

Objective To explore the protective effect of resveratrol on rat brain injury resulting from severe acute pancreatitis (SAP). Methods Ninety-six male Sprague-Dawley rats were randomly divided into four groups:sham-operation (SO) group,severe acute pancreatitis (SAP) group,resveratrol-treated (RES) group and dexamethasone-treated (DEX) group,with eight rats in each group evaluated at 3,6 and 12 h. Levels of serum myelin basic protein (MBP),tight junction protein zonula occludens 1 (Zo-1),TNF-? and IL-6 were determined by ELISA. The ultrastructural changes of the brain and pancreatic tissues were examined using a transmission electron microscope. Results MBP,Zo-1,TNF-? and IL-6 levels in RES group were lower than those in SAP group at all time points (P0.05). Conclusion The degradation of Zo-1 is involved in the pathophysiology of brain injury in SAP; MBP can be used as a marker of brain injury in SAP rats. Resveratrol can inhibit brain injury associated with SAP.

Objective To investigate the role of ischemic postconditioning(I-post) on intestinal mucosa in rats with ischemia-reperfusion (I/R) injury.Methods By using rat model of intestine I/R injury,32 male Sprague-Dawley rats were randomly divided into 4 groups: sham-operation group(S),I/R group(I/R),ischemic preconditioning group(IPC),and ischemic postconditioning group(I-post),respectively.The contents of malondialdehyde(MDA), the activity of superoxidase dismutase(SOD),and the activity of myeloperoxidase(MPO) in intestinal mucosa were measured respectively.The status of intestinal mucosa cellular apoptosis was detected by TdT-mediated dUTP-biotin nick end labeling(TUNEL).Chiu's count was used to assess the changes in intestinal pathological morphology.Results The content of MDA and activity of MPO were significantly reduced and the activity of SOD was enhanced in IPC group and I-post group compared with I/R group.There was obvious cellular apoptosis after reperfusion,and the apoptotic index in I-post group and IPC group was significantly lower than that in I/R group.Conclusion Ischemic postconditioning can result in protection against intestinal mucosa with I/R injury,which may be related to reducing the production of oxygen free radicals,maintaining the activities of antioxidant systems,and reducing intestinal mucosa cellular apoptosis.

Objective To investigate the effects of ischemic postconditioning (I-post) on intestinal mucosa mitochondrion after ischemia-reperfusion (IR) injury in rat intestine.Methods By using rat model of intestine IR injury,male Sprague-Dawley rats were divided into 4 groups:sham-operation group (S),IR group (IR),ischemic preconditioning group (IPC),and I-post group.Intestinal mucosa mitochondrial ultrastructural changes were observed by using transmission electron microscope (TEM).Mucosal cellular mitochondrial respiration function was studied by measuring the mitochondrial dehydrogenase-dependent reduction of MTT to its formazan derivative,and intestinal mucosal mitochondrial membrane potential was detected by confocal laser scanning microscopy.Results Compared with that in IR group,the injury of mitochondrion in I-post group and IPC group began to recover.The mitochondrial respiratory function and the mitochondrial membrane potential were significantly improved in I-post group and IPC group (P0.05).Conclusion The mechanism of ischemic postconditioning against IR injury of intestine in rats is partly related to maintaining the mitochondrial ultrastructural changes and respiratory function and improving mitochondrial membrane potential.

Objective To investigate the relationship between peritoneal macrophages (PMAs) and inflammatory reaction in a rat model of severe acute pancreatitis (SAP). Methods Sprague-Dawley rats were randomly divided into control group and SAP group. To induce SAP in rats, 40 g/L sodium taurocholate (0.1 mL/100 g) was injected into the pancreatic duct through retrograde exposure of pancreatic bile duct in hepatic porta. One-third of rats were sacrificed at 3, 6 or 12 h after modeling. PMAs were extracted, and incubated for 24 h in a humidified 5% carbon dioxide incubator. The expressions of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) mRNA in PMAs were measured by semi-quantitative RT-PCR. The levels of TNF-α and IL-1β in culture medium and serum were evaluated.The histological changes of pancreas were examined. Rosults The expressions of TNF-α mRNA and IL-1β mRNA in PMAs were significantly higher in SAP group than in control group at each time point (P<0.01). The concentrations of TNF-α and IL-1β in culture medium and serum were significantly elevated in SAP group compared with control group (P<0.01). The histological analysis of pancreas indicated that the damage was more severe in SAP group than in cuntrol group (P<0.01). Conclusion PMAs secrete cytokines into pancreatitis-associated ascitic fluid, and this study demonstrates a correlation between SAP and the activation of PMAs.

Objective To investigate the effect of fatty acid synthase (FASN)on apoptosis in pancreatic cancer cell PANC-1 and the possible molecular mechanism.Methods Annexin V/FITC and flow cytometry were performed to detect the expression of FASN in pancreatic cancer PANC-1 after C75 treatment and the change of apoptosis in pancreatic cancer cell PANC-1 treated with C75.Quantity reverse transcriptase polymerase chain reaction (RT-PCR)and Western blot were used to measure the protein and RNA expressions of Caspase-3,bcl-2 and FASN.Results Inhibited by C75,the activity of FASN in pancreatic cancer cell PANC-1 was significantly decreased.Meanwhile,PANC-1 showed an increased apoptosis level in a dose-dependent manner (P < 0.05 ). Furthermore,after C75 inhibited FASN in pancreatic cancer cells,the protein and RNA expressions of Caspase-3 significantly increased (P <0.05)whereas the level of Bcl-2 reduced (P <0.05).Conclusion FASN is involved in the process of apoptosis in PANC-1 via Bcl-2 and Caspase-3.Therefore,FASN will provide a new target for the treatment of pancreatic cancer and generate better treatment efficacy.

Objective The aim of this study is to demonstrate the diagnostic effect of brainstem evoked potential for pancreatic encephalopathy in rats with severe acute pancreatitis. Methods Sixty male Sprague-Dawley (SD) rats were randomly divided into two equal groups: a sham-operated (SO) group and a severe acute pancreatitis (SAP) group. Each group was evaluated at 3, 6, and 12 h during the experiment. To detect the brain stem evoked potential change at different time points. The ultrastructure of brain tissue was observed by transmission electron microscope (TEM). The expressions of the apoptosis-related proteins Bcl-2, Bax and caspase-3 were observed using immunohistochemical and Western Blot technique. Results In SAP group, congestion, edema, inflammatory cell infiltration, mitochondrial swelling and cell apoptosis were apparent. Compared with SO group, the brain stem evoked potential in severe acute pancreatitis group was obviously reduced in SAP group. Compared with SAP group, the expressions of Bcl-2 have increased, whereas the expressions of Bax and caspase-3 have decreased in SO group significantly ( <0.05) . Conclusion Brain stem evoked potential is a sensitive method in detection of rat brain damage. The results showed that the consistency and the damage degree of rats may be important clinical diagnostic index of pancreatic encephalopathy.