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1.
AIM: To establish a non-traumatic, easy to induce and reproducible mouse model of severe acute pancreatitis (SAP)induced with caerulein and lipopolyasccharide (LPS).METHODS: Thirty-two healthy mature NIH female mice were selected and divided at random into four groups (each of 8 mice), i.e., the control group (NS group), the caerulein group (Ch group), the lipopolysaccharide group (LPS group),and the caerulein+LPS group (Cn+LPS group). Mice were injected intraperitoneally with caerulein only, or LPS only,and caerulein and LPS in combination. All the animals were then killed by neck dislocation three hours after the last intraperitoneal injection. The pancreas and exo-pancreatic organs were then carefully removed for microscopic examination. And the pancreatic acinus was further observed under transmission electron microscope (TEM). Pancreatic weight, serum amylase, serum nitric oxide (NO)concentration, superoxide dismutase (SOD) and malondialdehyde (MDA) concentration of the pancreas were assayed respectively.RESULTS: (1) NS animals displayed normal pancreatic structure both in the exocrine and endocrine. In the LPS group, the pancreas was slightly edematous, with the infiltration of a few inflammatory cells and the necrosis of the adjacent fat tissues. All the animals of the Cn group showed distinct signs of a mild edematous pancreatitis characterized by interstitial edema, infiltration of neutrophil and mononuclear cells, but without obvious parenchyma necrosis and hemorrhage. In contrast, the Cn+LPS groupshowed more diffuse focal areas of nonviable pancreatic and hemorrhage as well as systemic organ dysfunction.According to Schmidt's criteria, the pancreatic histologic score showed that there existed significant difference in the Cn+LPS group in the interstitial edema, inflammatory infiltration,parenchyma necrosis and parenchyma homorrhage in comparison with those of the Cn group, LPS group and NS group (P<0.01 or P<0.05). (2) The ultrasturcture of acinar cells was seriously damaged in the Cn+LPS group. Chromatin margination of nuclei was present, the number and volume of vacuoles greatly increased. Zymogen granules (ZGs) were greatly decreased in number and endoplasmic reticulum exhibited whorls. The swollen mitochondria appeared, the crista of which was decreased in number or disappeared.(3) Pancreatic weight and serum amylase levels in the Cn +LPS was significantly higher than those of the NS group and the LPS group respectively (P<0.01 or P<0.05).However, the pancreatic wet weight and serum amylase concentration showed no significant difference between the Cn+LPS group and the Cn group. (4) NO concentration in the Cn+LPS group was significantly higher than that of NS group, LPS group and Cn group(P<0.05 or P<0.01). 5) The SOD and MDA concentration of the pancreas in the Cn+LPS group were significantly higher than those of NS, LPS and Cn groups (P<0.05 or P<0.01).CONCLUSION: The mouse model of severe acute pancreatitis could be induced with caerulein and LPS, which could be non-traumatic and easy to induce, reproducible with the same pathological characteristics as those of SAP in human, and could be used in the research on the mechanism of human SAP.  相似文献   

2.
3.
AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP).
METHODS: SAP rats were randomly assigned to the model group and treatment group while the normal rats were assigned to the sham operation group. The mortality, ascite volumes, ascites/body weight ratio and pancreas pathological changes of all rats were observed at 3, 6 and 12 h after operation. Their contents of amylase and endotoxin in plasma and contents of tumor necrosis factor (TNF-α), phospholipase A2 (PLA2) and IL-6 in serum were also determined. The microarray sections of their pancreatic tissues were prepared, terminal transferase dUTP nick end labeling (TUNEL) staining was performed and apoptotic indexes were calculated.
RESULTS: There was no marked difference between treatment group and model group in survival. The contents of amylase and endotoxin in plasma and contents of TNF-α, PLA2 and IL-6 in serum, ascite volumes, ascites/body weight ratio and pancreas pathological scores were all lower in treatment group than in model group to different extents at different time points [P 〈 0.05, 58.3 (26.4) ng/L vs 77.535 (42.157) ng/L in TNF-α content, 8.00 (2.00) points vs 9.00 (2.00) points in pathological score of pancreas respectively; P 〈 0.01, 0.042 (0.018) EU/mL vs 0.056 (0.0195) EU/mL in endotoxin content, 7791 (1863) U/L vs 9195 (1298) U/L in plasma amylase content, 1.53 (0.79) vs 2.38 (1.10) in ascites/body weight ratio, 8.00 (1.00) points vs 11.00 (1.50) points in pathological score of pancreas; P 〈 0.001, 3.36 (1.56) ng/L vs 5.65 (1.08) ng/L in IL-6 content, 4.50 (2.00) vs 7.20 (2.00), 4.20 (1.60) vs 6.40 (2.30), 3.40 (2.70) vs 7.90 (1.70) in ascite volumes, respectively]. The apoptotic indexes of pancreas head and pancreas tail were all higher in treatment group than in model group at 6 h [P 〈 0.01, 0.00 (2.00)% vs 0.00 (0.00)%,  相似文献   

4.
AIM To investigate the effects of combined use of emodin and baicalein(CEB) at the cellular and organism levelsin severe acute pancreatitis(SAP) and explore the underlying mechanism.METHODS SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in 48 male SD rats. Pancreatic histopathology score, serum amylase activity, and levels of tumour necrosis factor alpha(TNf-α), interleukin 6(IL-6), and IL-10 were determined to assess the effects of CEB at 12 h after the surgery. The rat pancreatic acinar cells were isolated from healthy male SD rats using collagenase. The cell viability, cell ultrastructure, intracellular free Ca2+ concentration, and inositol(1,4,5)-trisphosphate receptor(IP3 R) expression were investigated to assess the mechanism of CEB.RESULTS Pancreatic histopathology score(2.07 ± 1.20 vs 6.84 ± 1.13, P 0.05) and serum amylase activity(2866.2 ± 617.7 vs 5241.3 ± 1410.0, P 0.05) were significantly decreased in the CEB(three doses) treatment group compared with the SAP group(2.07 ± 1.20 vs 6.84 ± 1.13, P 0.05). CEB dose-dependently reduced the levels of the pro-inflammatory cytokines IL-6(466.82 ± 48.55 vs 603.50 ± 75.53, P 0.05) and TNF-α(108.04 ± 16.10 vs 215.56 ± 74.67, P 0.05) and increased the level of the anti-inflammatory cytokine IL-10(200.96 ± 50.76 vs 54.18 ± 6.07, P 0.05) compared with those in the SAP group. CEB increased cell viability, inhibited cytosolic Ca2+ concentration, and significantly ameliorated intracellular vacuoles and IP3 m RNA expression compared with those in the SAP group(P 0.05). There was a trend towards decreased IP3 R protein in the CEB treatment group; however, it did not reach statistical significance(P 0.05).CONCLUSION These results at the cellular and organism levels reflect a preliminary mechanism of CEB in SAP and indicate that CEB is a suitable approach for SAP treatment.  相似文献   

5.
Protective effects of rhubarb on experimental severe acute pancreatitis   总被引:8,自引:1,他引:7  
AIM:To investigate the effects of rhubarb on severe acutepancreatitis (SAP) in rats.METHODS:Severe acute pancreatitis was induced by twointraperitoneal injections of cerulein (40 μg/kg body weight)plus 5-h restraint water-immersion stress.Rhubarb (75-150 mg/kg) was orally fed before the first cerulein injection.The degree of pancreatic edema,serum amylase level,local pancreatic blood flow (PBF),and histologicalalterations were investigated.The effects of rhubarb onpancreatic exocrine secretion in this model were evaluatedby comparing with those of somatostatin.RESULTS:In the Cerulein Stress group,severe edemaand diffuse hemorrhage in the pancreas were observed,the pancreatic wet weight (11.60±0.61 g/Kg) and serumamylase (458 490±43 100 U/L) were markedly increased(P<0.01 vs control).In the rhubarb (150 mg/kg) treatedrats,necrosis and polymorphonuclear neutrophil (PMN)infiltration in the pancreas were significantly reduced(P<0.01),and a marked decrease (50%) in serum amylaselevels was also observed (P<0.01).PBF dropped to 38%(93±5 mL/min per 100 g) of the control in the Cerulein Stressgroup and partly recovered in the Cerulein Stress Rhubarb150 mg group (135±12 mL/min per 100 g) (P<0.01).Thepancreatic exocrine function was impaired in the SAP rats.The amylase levels of pancreatic juice were reduced in therats treated with rhubarb or somatostatin,comparing withthat of untreated SAP group.The bicarbonate concentration ofpancreatic juice was markedly elevated only in the rhubarb-treated group (P<0.01).CONCLUSION:Rhubarb can exert protective effects onSAP,probably by inhibiting the inflammation of pancreas,improving pancreatic microcirculation,and altering exocrinesecretion.  相似文献   

6.
AIM: To observe the effect of resveratrol on nuclear factor Kappa-B (NF-κB) activation and the inflammatory response in sodium taurocholate-induced pancreatitis in rats. METHODS: Seventy-two male SD rats were randomly divided into three groups: sham operation group (control), severe acute pancreatitis (SAP) group, and severe acute pancreatitis group treated with resveratrol (RES). A SAP model was established by injecting 4% sodium taurocholate 1 mL/kg through puncturing the pancreatic duct. In Res group, Res was given at 30 mg/kg b.m. intraperitoneally after the SAP model was successfully established. Eight animals from each group were sacrificed at 3, 6 and 12 h after modeling. The expression of NF-κB activation of pancreas was detected by irnmunohistochemical staining, whereas the levels of TNF-α and IL-8 in pancreatic tissues were estimated by radioimrnunoassay. The pathological changes of pancreas and lungs were examined microscopically. RESULTS: Much less hyperemia, edema, dust-colored necrotic focus and soaps were noticed in pancreas in RES group than in SAP group. In RES group, hemorrhage, exudates and infiltration of inflammatory cells in pancreas and interstitial edema, destruction of alveolar wall in lung were significantly less than in SAP group. In the SAP group, the activation of NF-κB in pancreatic tissues was enhanced significantly at any measure point compared with control group (64.23±10.72% vs 2.56±0.65%, 55.86±11.34% vs 2.32±0.42%, 36.23±2.30% vs 2.40±0.36%,P<0.01), TNF-α, IL-8 were also increased and reached their peak at 6 h and then declined. The activation of NF-κB and the levels of TNF-α and IL-8 in RES group were significantly lower than those in SAP group (P<0.01): activation (52.63±9.45% vs 64.23±10.72%, 40.52±8.40% vs 55.86±11.34%, 29.83±5.37% vs 36.23±2.30%), TNF-α (132.76±15.68 pg/mL vs 158.36±12.58 pg/mL, 220.32±23.57 pg/mL vs 247.67± 11.62 pg/mL, 175.68±18.43 pg/mL vs 197.35±12.57 pg/mL) and IL-8 (0.62±0.21 μg/L vs 0.83±0.10 μg/L, 1.10±0.124 μg/L vs1.32±0.18 μg/L, 0.98±0.16 μg/L vs 1.27±0.23μg/L). CONCLUSION: The activation of NF-KB is involved in the inflammatory response of rats with SAP. Resveratrol could effectively inhibit the expression of NF-κB activation, alleviate the severity of SAP through its anti-inflammatory effects and regulate the inflammatory mediators.  相似文献   

7.
Protective effects of rhubarb on experimental severe acute pancreatitis   总被引:9,自引:0,他引:9  
AIM: To investigate the effects of rhubarb on severe acute pancreatitis (SAP) in rats. METHODS: Severe acute pancreatitis was induced by two intraperitoneal injections of cerulein (40 μg/kg body weight) plus 5-h restraint water-immersion stress. Rhubarb (75-150 mg/kg) was orally fed before the first cerulein injection. The degree of pancreatic edema, serum amylase level, local pancreatic blood flow (PBF), and histological alterations were investigated. The effects of rhubarb on pancreatic exocrine secretion in this model were evaluated by comparing with those of somatostatin. RESULTS: In the Cerulein+Stress group, severe edema and diffuse hemorrhage in the pancreas were observed, the pancreatic wet weight (11.60&#177;0.61 g/Kg) and serum amylase (458 490&#177;43 100 U/L) were markedly increased (P&lt;0.01 vs control). In the rhubarb (150 mg/kg) treated rats, necrosis and polymorphonuclear neutrophil (PMN) infiltration in the pancreas were significantly reduced (P&lt;0.01), and a marked decrease (50%) in serum amylase levels was also observed (P&lt;0.01). PBF dropped to 38% (93&#177;5 mL/min per 100 g) of the control in the Cerulein+Stress group and partly recovered in the Cerulein+Stress+Rhubarb 150 mg group (135&#177;12 mL/min per 100 g) (P&lt;0.01). The pancreatic exocrine function was impaired in the SAP rats. The amylase levels of pancreatic juice were reduced in the rats treated with rhubarb or somatostatin, comparing with that of untreated SAP group. The bicarbonate concentration of pancreatic juice was markedly elevated only in the rhubarbtreated group (P&lt;0.01). CONCLUSION: Rhubarb can exert protective effects on SAP, probably by inhibiting the inflammation of pancreas, improving pancreatic microcirculation, and altering exocrine secretion.  相似文献   

8.
AIM:To observe the changes in interstitial cells of Cajal(ICC) in rats with experimental severe acute pancreatitis(SAP).METHODS:A total of twenty-four SD rats were randomly divided into two groups(n = 12),namely the sham(S) group and the SAP group;the SAP rat model was established by retrograde injection of 5% sodium taurocholate(1.0 mL/kg) into the pancreatic duct.Twenty-four hours later intestinal motility was assessed by testing small intestinal propulsion rate,and then the rats were sacrificed.The pancreas and jejunum were resected and underwent routine pathologic examination.Immunohistochemical staining was used to detect c-kit-positive cells in the jejunum.Expression of c-kit mRNA was detected by real-time polymerase chain reaction,and the expression of c-kit protein was evaluated by Western blotting.Ultrastructure of ICC was evaluated by transmission electron microscopy.RESULTS:There was bleeding,necrosis and a largeamount of inflammatory cell infiltration in pancreatic tissue in the SAP group,while in jejunal tissue we observed a markedly denuded mucosal layer,loss of villous tissue and a slightly dilated muscular layer.The small intestinal propulsion rate was 68.66% ± 2.66% in the S group and 41.55% ± 3.85% in the SAP group.Compared with the S group,the rate of the SAP group decreased sharply.The density of c-kit-positive cells in the SAP group was significantly lower than in the S group;the respective mean densities were 88.47 ± 10.49 in the S group and 56.11 ± 7.09 in the SAP group.The levels of c-kit protein and mRNA were 0.36 ± 0.04 and 1.29 ± 0.91 in the SAP group,respectively,which were significantly lower than those in the S group(0.53 ± 0.06,0.64 ± 0.33,respectively).In the SAP group,ICC profiles showed the same change tendency,such as vacuolation of mitochondria,irregular vacuoles and loosened desmosome-like junctions.CONCLUSION:Decreased c-kit-positive cells and ultrastructural changes in ICC resulting from blockade of the c-kit signaling pathway are involved in the intestinal dysmotil  相似文献   

9.
AIM: To observe the therapeutic efficacy of Baicalin in rats with severe acute pancreatitis (SAP) and explore its therapeutic mechanisms. METHODS: The SAP rat models were randomly divided into the model control group, Baicalin treatment group, octreotide treatment group and sham operation group. All groups were randomly subdivided into 3 h, 6 h and 12 h groups with 15 rats in each group. The survival, ascites volume and pathological changes of pancreas in all rats were observed at different time points after operation. The plasma amylase content and serum TNF-α, IL-6, malonaldehyde (MDA) and PLA2 contents were also determined. RESULTS: The survival was not obviously different between the treated groups, and was significantly higher in treated groups at 12 h compared to the model control group (P 〈 0.05, 15 vs 10). The ascites/body weight ratio at 3 h and 6 h was significantly lower in Baicalin treatment group compared to the model control group and octreotide treatment group (P 〈 0.05, 1.00 vs 2.02 and 1.43 and P 〈 0.001, 2.29 (1.21) vs 2.70 (0.80) and 2.08 (2.21), respectively). The contents of amylase, TNF-α, IL-6, MDA and PLA2 were significantly lower in the treated groups than in the model control group (P 〈 0.05, 4342 vs 5303, 5058 vs 6272 in amylase, P 〈 0.01, 21.90 vs 36.30, 23.80 vs 39.70, 36 vs 54.35 in MDA and 56.25 vs 76.10 in PIA2, or P 〈 0.001, 65.10 and 47.60 vs 92.15 in TNF-α, 3.03 vs 5.44, 2.88 vs 6.82, 2.83 vs 5.36 in IL-6, respectively). The pathological scores of pancreas in the treated groups were significantly lower than that in the model control group (P 〈 0.05, 9.00 vs 10.05, 6.00 vs 9.00, 8.00 vs 10.05), but no marked difference was found between the treated groups. CONCLUSION: The Baicalin injection has significant therapeutic effects on SAP rats, its effects are similar to those of octreotide. The Baicalin injection is also cheap and has a big application range, quite hopefully to be used in clinical treatment of SAP.  相似文献   

10.
AIM: To observe the effect of proteasome inhibitor MG-132 on severe acute pancreatitis (SAP) and associated lung injury of rats. METHODS: Male adult SD rats were randomly divided into SAP group, sham-operation group, and MG-132 treatment group. A model of SAP was established by injection of 5% sodium taurocholate into the biliary- pancreatic duct of rats. The MG-132 group was pretreated with 10 mg/kg MG-132 intraperitoneally (ip) 30 min before the induction of pancreatitis. The changes in serum amylase, myeloperoxidase (MPO) activity of pancreatic and pulmonary tissue were measured. The TNF-α level in pancreatic cytosolic fractions was assayed with an enzyme-linked immunosorbent assay (ELISA) kit. Meanwhile, the pathological changes in both pancreatic and pulmonary tissues were also observed. RESULTS: MG-132 significantly decreased serum amylase, pancreatic weight/body ratio, pancreatic TNF-α level, pancreatic and pulmonary MPO activity (P 〈 0.05). Histopathological examinations revealed that pancreatic and pulmonary samples from rats pretreated with MG-132 demonstrated milder edema, cellular damage, and inflammatory activity (P 〈 0.05). CONCLUSION: The proteasome inhibitor MG-132 shows a protective effect on severe acute pancreatitis and associated lung injury of rats.  相似文献   

11.
AIM: To investigate the mechanism of resveratrol underlying the microcirculation disorder and lung injury following severe acute pancreatitis (SAP). METHODS: Twenty-four rats were divided into 3 groups (SAP, sham and resveratrol groups) randomly. SAP model was established by injecting 4% sodium taurocholate l mL/kg through puncturing pancreatic ducts. Sham (control) group (8 rats) was established by turning over the duodenum. Resveratrol was given at 0.1 mg/kg b.m. intraperitoneally. Rats were sacrificed 9 h after SAP was induced. Blood samples were obtained for hemorrheological examination. Lung tissues were used for pathological observation, and examination of microvascular permeability, dry/wet ratio and myeloperoxidase (MPO) activity. Gene expression of intercellular adhesion molecule-1 (ICAM-1) was detected by RT-PCR. RESULTS: Compared with SAP group, resveratrol relieved the edema and infiltration of leukocytes in the lungs. Resveratrol improved markers of hemorrheology: high VTB (5.77±1.18 mPas vs9.49±1.34 mPas), low VTB (16.12±3.20 mPas vs30.91±7.28 mPas), PV (4.69±1.68 mPas vs 8.00±1.34 mPas), BSR (1.25±0.42 mm/h vs50.03±0.03 mm/h), VPC (54.67±3.08% vs 62.17±3.39%), fibrinogen (203.2?7.8 g/ L vs 51.3±19.1 g/L), original hemolysis (0.45±0.02 vs 0.49±0.02), and complete hemolysis (0.41±0.02 vs 0.43±0.02) (P<0.05). Resveratrol decreased the OD ratio of ICAM-1 gene (0.800±0.03 vs 1.188±0.10), dry/wet ratio (0.74±0.02 vs 0.77±0.03), microvascular permeability (0.079±0.006 vs 0.112±0.004) and MPO activity (4.42±0.32 vs 5.03±0.51) significantly (P<0.05). CONCLUSION: Resveratrol can improve the microcirculation disorder of the lung by decreasing leukocyte-endothelial interaction, reducing blood viscosity, improving the decrease of blood flow, and stabilizing erythrocytes in SAP rats. It may be a potential candidate to treat SAP and its severe complications (ALI).  相似文献   

12.
AIM: To observe the therapeutic effects of dexamethasone on rats with severe acute pancreatitis (SAP) and investigate the influences of dexamethasone on the inflammatory mediators and NF-κB expression in multiple organs of SAP rats as well as the mechanisms involved.
METHODS: Ninety Sprague-Dawley (SD) rats with SAP were randomly divided into the model group (n = 45) and dexamethasone treatment group (n = 45), and another 45 rats were selected for the sham operation group. All groups were randomly subdivided into the 3 h, 6 h and 12 h groups, each group containing 15 rats. The survival of all groups and pathological changes of multiple organs (liver, kidney and lung) were observed at different time points after the operation. The pathological score of multiple organs was carried out, followed by the determination of amylase, endotoxin and TNF-α contents in blood. The tissue microarray was used to detect the expression levels of NF-κB p65 protein in multiple organs. RESULTS: There was no marked difference between the model group and treatment group in the survival rate. The amylase content,of the treatment group was significantly lower compared to the model group at 12 h (P 〈 0.01, 7791.00 vs 9195.00). Moreover, the endotoxin and TNF-α levels of the treatment group were significantly lower than that of the model group at 6 h and 12 h (P 〈 0.01, 0.040 vs 0.055, 0.042 vs 0.059 and P 〈 0.05, 58.30 vs 77.54, 38.70 vs 67.30, respectively). Regarding the changes in liver NF-κB expression, the model group significantly exceeded the sham operation group at 3 h (P 〈 0.01, 1.00 vs 0.00), and the treatment group significantly exceeded the sham operation group at 12 h (P 〈 0.01, 1.00 vs 0.00), whereas no marked difference was observed between the model group and treatment group at all time points. The kidney NF-κB expression level in the treatment group significantly exceeded the model group (P 〈 0.05, 2.00 vs 0.00) and the sham operation group (P 〈 0.01, 2  相似文献   

13.
Background Our aim was to investigate the changes of mitogen-activated protein kinases (MAPKs) by activated protein C (APC) treatment in rats with severe acute pancreatitis (SAP), and relate them to changes in SAP severity, thus providing evidence for developing clinical therapies. Methods Sprague-Dawley rats were given an intravenous injection of saline (SAP group), APC (50 μg/kg or 10 μg/kg), or CNI1493 just before SAP induction. One group of rats underwent a sham operation (control group). Experimental samples were harvested 16 h after SAP induction. The gene expression of pancreatic MAPKs was evaluated by cDNA microarrays. The mRNA and protein/phosphorylated protein levels of p38 MAPK, extracellular signal-regulated protein kinase (ERK) 1/2, and c-Jun N-terminal kinase (JNK) and the protein levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were determined in pancreatic tissue. The severity of disease was evaluated by pancreatic histology, the pancreatic wet/dry weight ratio, and the serum amylase level. Results In rats treated with APC (50 μg/kg) or CNI1493, the severity of pancreatitis and expression of pancreatic TNF-α and IL-1β proteins were attenuated by the decreased expression and activity of p38 MAPK and JNK (vs. the SAP group, P < 0.01). The expression and activity of ERK1/2 were increased in APC-treated rats, especially in the group treated with APC 50 μg/kg (vs. the SAP or CNI1493-treated group, P < 0.01, respectively). Conclusions Inhibition of expression of pancreatic p38 MAPK and JNK and upregulation of ERK1/2 expression by APC treatment may protect against pancreatic injury, thus ameliorating severity of the disease.  相似文献   

14.
AIM:To investigate the dynamic changes and significance of platelet activating factor receptor (PAF-R) mRNA and protein in pancreatic tissues of rats with severe acute pancreatitis (SAP) and effects of BN52021 (Ginkgolide B). METHODS:Wistar male rats were randomly assigned to the negative control group (NC group),SAP model group (SAP group),and BN52051-remedy group (BN group),and each of the groups was divided into 6 subgroups at different time points after operation (1 h,2 h,3 h,6 h,12 h,and 24 h) (n=10 in each). PT-PCR and Western blot methods were used to detect PAF-RmRNA and protein expression in pancreatic tissues of rats respectively. Pathological examination of pancreatic tissues was performed and the serum amylase change was detected. RESULTS:Serum amylase and pathological results showed the that SAP model was successfully prepared,BN52021 was able to decrease serum amylase,and the pathological ratings in BN group at 3 h,6 h,and 12 h significantly decreased compared with those in the SAP group (8.85 ± 0.39 vs 5.95 ± 0.19,9.15 ± 0.55 vs 5.55 ± 0.36,10.10 ± 0.65 vs 6.72 ± 0.30,P < 0.05). The result of PAF-mRNA showed dynamic changes in SAP and BN groups,which increased gradually in early stage,reached a peak at 3 h (0.71 ± 0.14 vs 0.54 ± 0.14,0.69 ± 0.13 vs 0.59 ± 0.04,P < 0.05),and decreased gradually later. There were significant differences at each time point except 1 h and 2 h,when compared with those in the NC group (0.71 ± 0.14 or 0.69 ± 0.13 vs 0.47 ± 0.10,0.38 ± 0.08 or 0.59 ± 0.04 vs 0.47 ± 0.09,0.25 ± 0.07 or 0.29 ± 0.05 vs 0.46 ± 0.10,0.20 ± 0.06 or 0.20± 0.04 vs 0.43 ± 0.09,P < 0.05),whereas there was no significant difference between BN and SAP groups at each time point. The result of PAF-R protein showed that the change of PAF-R protein in the SAP group and the BN group was consistent with that of PAF-R mRNA. There were significant differences at each time point except 1 h,when compared with those in the NC group (0.90 ± 0.02 or 0.80 ± 0.05 vs 0.48 ± 0.02,1.69 ± 0.06 or 1.58 ± 0.02 vs 0.48 ± 0.03,1.12 ± 0.10 or 0.98 ± 0.03 vs 0.49 ± 0.09,1.04 ± 0.14 or 0.87 ± 0.02 vs 0.52 ± 0.08,0.97 ± 0.16 or 0.90 ± 0.05 vs 0.49 ± 0.10,P < 0.05),whereas there was no significant difference between the BN group and the SAP group. CONCLUSION:PAF-R plays an important role in occurrence and development of SAP. BN52021 exerts biological effects through competitively inhibiting the binding of increased both PAF and PAF-R expression rather than through decreasing PAF-R expression in pancreatic tissues.  相似文献   

15.
目的 探讨吡格列酮预处理对ANP大鼠的影响.方法 54只大鼠采用经胆胰管逆行注射5%牛磺胆酸钠制备ANP模型.大鼠按随机数字法分为ANP组、吡格列酮组和假手术组,各18只.吡格列酮组在制模前2 h腹腔注射0.2%吡格列酮20 mg/kg体重.分别在术后3 h、6 h、12 h处死动物,取血检测血淀粉酶,取胰腺组织观察胰腺大体及组织学变化,分别按Hushes和Kusske标准评分.结果 术后3 h、6 h、12 h,ANP组及吡格列酮组血淀粉酶、胰腺大体病理的Hughes评分和胰腺组织学Kusske评分比假手术组明显升高;吡格列酮组大鼠术后12 h血淀粉酶、胰腺Hughes评分和Kusske评分分别为(2 980±1 080)U/L、4.50±2.07和7.50±1.05,均明显低于ANP组的(7 598±1 072)U/L、7.17±1.47和11.33±1.75(P<0.01).结论 吡格列酮预处理可降低ANP大鼠血清淀粉酶,减轻胰腺大体、组织学病理改变,说明吡格列酮具有预防ANP的效应.  相似文献   

16.
AIM: To investigate the effect of delayed ethyl pyruvate (EP) delivery on distant organ injury, survival time and serum high mobility group box 1 (HMGB1) levels in rats with experimental severe acute pancreatitis (SAP).
METHODS: A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups (n = 32 in each group): sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP (30 mg/kg) at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate arninotransferase (AST), alanine arninotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) levels were measured. Lung wet-to-dry-weight (W/D) ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the influence of EP on survival times of SAP rats.
RESULTS: Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios (8.22 ±0.42 vs 9.76 ± 0.45, P 〈 0.01), pulmonary histological scores (7.1 ± 0.7 vs 8.4 ± 1.1, P 〈 0.01), serum AST (667 ± 103 vs 1 368 ± 271, P 〈 0.01), ALT (446 ± 91 vs 653 ± 98, P 〈 0.01) and Cr (1.2 ± 0.3 vs 1.8 ± 0.3, P 〈 0.01) levels. SAP rats had a median survival time of 44 h. Delayed EP treatment significantly prolonged median survival time to 72 h (P 〈 0.01).
CONCLUSION: Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGBllevels in rats with experimental SAP. EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome (MODS) in SAP patients.  相似文献   

17.
徐萍  娄晓丽  陈诚 《胰腺病学》2013,(6):395-398
目的 探讨吡格列酮在重症急性胰腺炎发病机制中与凋亡激活的关系.方法 将80只SD大鼠按随机表法分为急性坏死性胰腺炎组(ANP组)、假手术组、二甲基亚砜溶剂对照组(DMSO组)、吡格列酮干预组(吡格列酮组),每组20只.采用胰胆管逆行注射5%牛磺胆酸钠1 ml/kg体质量的方法制作ANP模型,吡格列酮组在造模前30 min腹腔注射吡格列酮40 mg/kg体质量.术后1、3、6、12 h分批处死大鼠,收集胰腺组织.采用常规HE染色进行胰腺组织病理评分,采用TUNEL染色方法检测大鼠胰腺细胞凋亡,免疫组化法和蛋白质印迹法检测胰腺组织PPARγ的表达变化,同时检测胰腺组织caspase3的表达变化.结果 吡格列酮干预后大鼠胰腺组织病理损伤较ANP组大鼠有所减轻,差异有统计学意义(P<0.05).吡格列酮组胰腺组织PPARγ表达水平为2.69 ±0.46,显著高于ANP组的0.75 ±0.05,差异有统计学意义(P<0.05).吡格列酮3h组大鼠胰腺细胞凋亡指数为8.35 ±0.95,显著高于同时点ANP组的4.37±1.22;caspase 3的活性为9.24±1.78,显著高于ANP组的5.04±0.86,差异均有统计学意义(P值均<0.05).结论 吡格列酮干预后大鼠胰腺炎症减轻,PPARγ和caspase 3表达升高,胰腺细胞凋亡率升高.  相似文献   

18.
目的 探讨核因子κB (NF κB)和细胞间粘附分子 1 (ICAM 1 )在吸烟大鼠气道上皮细胞中表达的变化及其在气道炎症形成过程中的作用。方法 Wistar大鼠 39只 ,随机分为不吸烟组、吸烟1个月组、3个月组 ,每组 1 3只。采用免疫组织化学染色和原位杂交技术半定量检测各组NF κB亚单位p65和ICAM 1的表达。结果  (1 )吸烟 1个月组、3个月组细支气管上皮细胞NF κB核染色阳性细胞百分比为 (63± 4) %、(51± 5) % ,与不吸烟组 [(2 7± 5) % ]比较 ,差异有显著性 (P分别 <0 .0 1 ) ;(2 )吸烟 1个月组、3个月组主、细支气管气道上皮细胞ICAM 1mRNA的表达为 0 .645± 0 .0 38、0 .747±0 0 4 1、0 .688± 0 .0 62、0 .80 9± 0 .0 2 3 ,与不吸烟组 (0 .52 6± 0 .0 2 3、0 .635± 0 .0 4 4 )比较差异有显著性 (P分别 <0 .0 1 ) ;而且 3个月组与 1个月组比较差异也有显著性 (P分别 <0 .0 5、0 .0 1 ) ;(3)吸烟 1个月组、3个月组主、细支气管气道上皮细胞ICAM 1蛋白表达为 0 .73± 0 .0 4、0 .94± 0 .0 5、0 .77± 0 .0 4、0 .99± 0 .0 3 ,与不吸烟组 (0 .57± 0 .0 4、0 .83± 0 .0 4 )比较 ,差异也有显著性 (P分别 <0 .0 1 ) ;而且 3个月组与 1个月组比较差异也有显著性 (P分别 <0 .0 5) ;(4)各组细支气管上皮  相似文献   

19.
DU RQ  Li HL  Yang WY  Xiao JZ  Wang B  Lou DJ  Bai XP  Pan L 《中华内科杂志》2007,46(8):661-665
目的探讨高脂饲养大鼠胰岛α细胞炎症通路分子基因的表达变化及吡格列酮干预的影响。方法8周龄雄性SD大鼠随机分为3组(每组15只):正常饲养组(NC)、高脂饲养组(HF)、高脂+吡格列酮组(HP)。喂养20周后检测空腹血胰岛素(Fins)、胰高血糖素(Glc)、游离脂肪酸(FFA)、高敏C反应蛋白(hsCRP)水平;正常血糖高胰岛素钳夹试验评价外周胰岛素抵抗程度;离体胰岛细胞表面灌注检测高糖状态Glc分泌的动态变化,同时3组大鼠各随机人组8只给予大剂量链脲菌素去β细胞处理,分为正常去β细胞组(NC-B),高脂去β细胞组(HF-B),高脂+吡格列酮去母细胞组(HP—B),采用定量PCR方法比较3组去母细胞大鼠α细胞NF-κB、NF-κB抑制蛋白α(IκBα)mRNA表达的情况。结果(1)HF组葡萄糖输注率(GIR)明显低于NC组,血Fins、Glc、FFA及hsCRP水平均显著高于NC组;而HP组以上各项指标较HF组均明显改善。(2)胰岛细胞表面灌注,HF组基础Glc的分泌高于NC组(P〈0.01),16.7mmol/L葡萄糖灌注后HF组胰岛的Glc分泌未受抑制,HP组与NC组比较差异无统计学意义。(3)与NC-B组相比,HF-B组α细胞NF-κB mRNA的表达增高20.5%,IκBα mRNA表达降低24.3%(P值均〈0.01)。HP-B组较HF.B组NF-κB、IκBα mRNA分别改善78.3%、58.8%。(4)HF组血FFA水平与GIR呈负相关(r=-0.675,P〈0.01);与NF-κB mRNA表达呈正相关(r=0.775,P〈0.05)。结论高脂饲养导致胰岛α细胞胰岛素抵抗,同时激活了α细胞炎症通路基因的表达且与FFA升高有关。吡格列酮干预能改善上述变化。  相似文献   

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