重组人Elafin对实验性大鼠急性胰腺炎作用的研究
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摘要
急性胰腺炎(Acute pancretitis,AP)是一种炎症性疾病,基本病理改变为胰腺腺泡的急性损害和胰腺的急性炎症,炎症不仅涉及胰腺局部,而且会发生全身性炎症反应。急性胰腺炎发病急、病情凶险、病死率高,早期容易并发多脏器功能衰竭,尤其是急性肺损伤(ALI)。急性肺损伤是一种肺泡毛细血管膜弥散性损伤,导致肺水肿和肺不张,进一步发展即为急性呼吸窘迫综合征(ARDS)。ALI和ARDS是AP最常见和最严重的全身并发症之一,也是致死的主要原因。AP和AP并发ALI发病机制复杂。
Elafin称弹性蛋白酶特异性抑制因子,是支气管Clara细胞、II型肺泡上皮细胞及肺泡巨噬细胞等在炎性刺激诱导下表达。Elafin为中性粒细胞弹性蛋白酶、胰弹性蛋白酶、蛋白酶3等丝氨酸蛋白酶特异性抑制剂。炎性反应是机体对损伤的一种保护性反应,其目的是将损伤源破坏、稀释并清除,与此同时也会引起不同程度的自身损伤。中性粒细胞弹性蛋白酶被认为是炎性反应的主要终效应因子,Elafin是内源性的弹性蛋白酶抑制剂,具有抗蛋白酶活性、抗炎活性和直接的抗微生物活性等重要作用。本研究首先利用牛磺胆酸钠逆行胆胰管注射法建立大鼠急性胰腺炎和胰腺炎合并肺损伤模型,之后给与重组人Elafin,通过急性胰腺炎大鼠血清生化指标检测,观察胰腺组织和肺组织病理学变化,考察重组人Elafin对大鼠急性胰腺炎及合并肺损伤的作用,对其作用机制进行探讨。
本论文的创新之处在于:1)证实了Elafin对实验性大鼠急性胰腺炎的治疗作用,并对其作用机制进行探讨。2)证实了Elafin对实验性大鼠急性胰腺炎合并肺损伤的治疗作用,并对其作用机制进行探讨。国内外尚未见Elafin对大鼠急性胰腺炎和胰腺炎合并肺损伤作用的报道。
Acute necrosis pancreatitis is one of the common severe clinical diseases with many complications, high mortality, the complicated causes and pathophysiological changes and the unclear mechanism. Leukocytes over-activity hypothesis consider that Cascade Effect induced by cytokines and the whole body leukocytes activation mediated by cytokines lead to the over-activity of Systemic Inflammatory Response Syndrome (SIRS),and this cause the damage of distant organs, the multiple organ dysfunction syndrome(MODS),and even the multiple organ system failure(MSOF).
Acute lung injury (ALI) is one of the common complications. Most of the patients died combined with lung injury or died of severe lung injury. The mechanism of pancreatitis-associated lung injury is complicated. In recent years, most researches focus on the activation pathway of the inflammatory cells and mediators and consider that lung injury is the local manifestation of SIRS in lung, and the inflammatory injury is easy to occur in lung for its tissue specificity.
Recombinant human elafin is an elastase inhibitor with the Mr of 6kDa, and its gene located on chromosome 20. Elafin is the specific inhibitor of neutrophil elastase (NE), pancreatic elastase and proteinase 3.Elafin inhibits the activity of serine proteases, and then plays its role in adjusting the release of inflammatory meditors, inhibiting the transendothelial migration of leukocytes and the activation of hemacytes, reducing the infiltration of inflammatory cells and the release of tissue toxic substances, etc. From this we can see that elafin display its multi-layered anti-inflammatory effect. Elafin has attracted clinic widespread attention by its protective effect through anti-inflammatory.
This suggests that elafin inhibits the pancreatic exocrine and pancreatin activity, such as the activity of pancreatic elastase, thus prevent the pancreatic tissue from the direct damage and blood vessel injury of actived elatase. Moreover, elafin inhibits the release of inflammatory cells and mediators, thus exert its function on defending or curing the pancreatitis.
This paper established the model of rat acute pancreatitis by using retrograde injection of Sodium Taurocholate into cholangiopancreatic duct, and then we observed the protective effects of elafin on rats acute pancreatitis by biochemical and pathological changes of rats after elafin treatment. In the last we will discuss the mechanism of pancreatitis.
Test 1 the effects of recombinant human elafin on experimental acute pancreatitis in rats
Rats were done with abdominal operation after anesthesia of 3% pentobarbital sodium, and then infused slowly 3.5% sodium taurocholate 0.1mg/100g in cholangiopancreatic duct t, whereas control group were infused the same amount physiological saline. Rats were randomly divided into six groups: the blank group (NS group), the model group (ANP+NS group) and the high-dose elafin group, the medium-dose group, the low-dose group, the positive control group, with 10 rats in each group. In addition of tosodium taurocholate, the high,medium,low-dose elafin groups received intravenous infusion of (5IU/kg、10IU /kg、20IU/kg)elafin, while the control and model group received the same amount of physiological saline, with the period of every 8 hours one infusion , continuously 6 times . 48 hours after the last injection, the blood samples from the abdominal aorta were obtained, then the serum NO, SOD,LPO, content were detected; After the pancreatic tissue homogenate, the tissue protein, amylase, lipase, SOD,LPO content were detected; pathological changes of rats pancreatic tissue were observed and its morphological structure were observed by electron microscope.
Test 1 Results
1 The changes of Amylase and Lipase of serum and pancreatic tissue: After treatment, serum and pancreatic tissue amylase and lipase in model group increased significantly(p<0.001), Compared with the model group,serum amylase and lipase of elafin(low dose, medium dose, high dose) groups decreased significantly (p<0.05, p<0.01 or p<0.001). The effect of high dose group is almost equal to aprotinin group.
2 The changes of SOD and LPO of serum and pancreatic tissue and the serum NO:
The serum and pancreatic tissue SOD in model group decreased significantly(p<0.001 ) . while the content of LPO and NO increased significantly(p<0.001). The serum and pancreatic tissue SOD in elafin(low dose, medium dose, high dose) groups increased significantly(p<0.001). while the content of LPO and NO decreased significantly(p<0.001). The effect of high dose group is almost equal to aprotinin group.
3 Morphological Changes of the Pancreatic Tissue;
In the model group, bloodyascites, necrotic foci in pancreas, and fat necrosis in mesentery and omentum was found grossly. Interstitial lobular inflammatory infiltrations were observed in pancreas microscopically, as well as diffusive bleeding and piecemeal necrosis. In elafin (low dose, medium dose, high dose) groups, ascites and fat necrosis diminished notably compared with those in the model group. Microscopically, slight bleeding, mild acinar degeneration and mild structure damage to lobules were observed together with declining inflammatory infiltration. The results show that the pathological changes significantly become light after elafin treatment.
4 The expression of TNF-α、NF-κB in Pancreatic Tissue In the model group, there are many positive cells which can express TNF-α、NF-κB in the pancreatic tissue, while few exists in the elafin (low dose, medium dose, high dose) groups.
Test 2 The effects of recombinant human elafin on experimental acute pancreatitis-associated lung injury in rats Rats were done with abdominal operation after anesthesia of 3% pentobarbital sodium, and then infused slowly 3.5% sodium taurocholate 0.1mg/100g in cholangiopancreatic duct t, whereas control group were infused the same amount physiological saline. Rats were randomly divided into six groups: the blank group (NS group), the model group (ANP+NS group) and the high-dose elafin group, the medium-dose group, the low-dose group, the positive control group, with 10 rats in each group. In addition of tosodium taurocholate, the high,medium,low-dose elafin groups received intravenous infusion of (2μg/kg、4μg /kg、8μg /kg)elafin, while the control and model group received the same amount of physiological saline, with the period of every 8 hours one infusion , continuously 6 times . 48 hours after the last injection, the lung W/D ratio was measured; the protein content of BALF was detected with Coomassie Breiliant Blue; after the lung tissue homogenate, the t TNF-α, MPO content were measured; pathological changes of rats lung tissue were observed and its morphological structure were observed by electron microscope.
Test 2 Results
1 The changes of lung W/D ratio and the protein of BALF Compared with the blank group, the lung W/D ratio and the protein of BALF in the model group increased significantly (p<0.001); Compared with the model group, the lung W/D ratio and the protein of BALF in the elafin (low dose, medium dose, high dose) groups decreased significantly(p<0.05, p<0.01 or p<0.001). The effect of high dose group is almost equal to aprotinin group.
2 The changes of TNF-α, MPO content in the lung tissue Compared with the blank group, the lung TNF-α, MPO content in the model group increased significantly (p<0.001); Compared with the model group, the lung TNF-α, MPO content in the elafin (medium dose, high dose) groups increased significantly(p<0.05, p<0.01). The effect of high dose group is almost equal to aprotinin group.
3 Morphological Changes of the Lung Tissue;
The blank group: the clear lung structure and the slim alveolar wall were observed; and there was no polymorph nuclear neutrophils infiltration. The model group: there were many neutrophils infiltration in the interstitial lung, especially around the vessel and little bronchus. The pulmonary edema became serious; part of the alveolus space was seen to be filled with effusion and neutrophils; alveolar septum significantly became broad. Compared with the model group, alveolar septum of the elafin (low dose, medium dose, high dose) groups significantly became slim; the infiltration of neutrophils significantly became less.
The above results show that elafin can significantly reduce serum amylase and lipase in AP group; inhibit the activation of pancreatic elastase and improve the hypersecretion in the pancreatitis. Elafin can reduce LPO of serum and pancreatic tissue rapidly and increase the SOD activity of serum and pancreatic tissue in acute pancreatitis, this suggests that elafin can improve its antioxidant activity by inhibiting lipid peroxide. Elafin can significantly inhibit the release of serum NO and prevent the interaction between inflammatory mediators and leukocytes, thus alleviate the development of acute pancreatitis. In the meantime, elafin can significantly reduce the lung W/D ratio and the protein of BALF and the lung TNF-α, MPO content in the pancreatitis-associated lung injury. According to the pathological observation, elafin can significantly reduce the edema, hemorrhage, and necrosis of pancreatic tissue, this suggest that it has the function of improving the organism repair capacity and protecting organs. Elafin can significantly reduce the infiltration of inflammatory cells in the lung and make the alveolar wall slim.
In conclusion, elafin can prevent and cure the acute pancreatitis and the acute pancreatitis-associated lung injury.
Elafin称弹性蛋白酶特异性抑制因子,是支气管Clara细胞、II型肺泡上皮细胞及肺泡巨噬细胞等在炎性刺激诱导下表达。Elafin为中性粒细胞弹性蛋白酶、胰弹性蛋白酶、蛋白酶3等丝氨酸蛋白酶特异性抑制剂。炎性反应是机体对损伤的一种保护性反应,其目的是将损伤源破坏、稀释并清除,与此同时也会引起不同程度的自身损伤。中性粒细胞弹性蛋白酶被认为是炎性反应的主要终效应因子,Elafin是内源性的弹性蛋白酶抑制剂,具有抗蛋白酶活性、抗炎活性和直接的抗微生物活性等重要作用。本研究首先利用牛磺胆酸钠逆行胆胰管注射法建立大鼠急性胰腺炎和胰腺炎合并肺损伤模型,之后给与重组人Elafin,通过急性胰腺炎大鼠血清生化指标检测,观察胰腺组织和肺组织病理学变化,考察重组人Elafin对大鼠急性胰腺炎及合并肺损伤的作用,对其作用机制进行探讨。
本论文的创新之处在于:1)证实了Elafin对实验性大鼠急性胰腺炎的治疗作用,并对其作用机制进行探讨。2)证实了Elafin对实验性大鼠急性胰腺炎合并肺损伤的治疗作用,并对其作用机制进行探讨。国内外尚未见Elafin对大鼠急性胰腺炎和胰腺炎合并肺损伤作用的报道。
Acute necrosis pancreatitis is one of the common severe clinical diseases with many complications, high mortality, the complicated causes and pathophysiological changes and the unclear mechanism. Leukocytes over-activity hypothesis consider that Cascade Effect induced by cytokines and the whole body leukocytes activation mediated by cytokines lead to the over-activity of Systemic Inflammatory Response Syndrome (SIRS),and this cause the damage of distant organs, the multiple organ dysfunction syndrome(MODS),and even the multiple organ system failure(MSOF).
Acute lung injury (ALI) is one of the common complications. Most of the patients died combined with lung injury or died of severe lung injury. The mechanism of pancreatitis-associated lung injury is complicated. In recent years, most researches focus on the activation pathway of the inflammatory cells and mediators and consider that lung injury is the local manifestation of SIRS in lung, and the inflammatory injury is easy to occur in lung for its tissue specificity.
Recombinant human elafin is an elastase inhibitor with the Mr of 6kDa, and its gene located on chromosome 20. Elafin is the specific inhibitor of neutrophil elastase (NE), pancreatic elastase and proteinase 3.Elafin inhibits the activity of serine proteases, and then plays its role in adjusting the release of inflammatory meditors, inhibiting the transendothelial migration of leukocytes and the activation of hemacytes, reducing the infiltration of inflammatory cells and the release of tissue toxic substances, etc. From this we can see that elafin display its multi-layered anti-inflammatory effect. Elafin has attracted clinic widespread attention by its protective effect through anti-inflammatory.
This suggests that elafin inhibits the pancreatic exocrine and pancreatin activity, such as the activity of pancreatic elastase, thus prevent the pancreatic tissue from the direct damage and blood vessel injury of actived elatase. Moreover, elafin inhibits the release of inflammatory cells and mediators, thus exert its function on defending or curing the pancreatitis.
This paper established the model of rat acute pancreatitis by using retrograde injection of Sodium Taurocholate into cholangiopancreatic duct, and then we observed the protective effects of elafin on rats acute pancreatitis by biochemical and pathological changes of rats after elafin treatment. In the last we will discuss the mechanism of pancreatitis.
Test 1 the effects of recombinant human elafin on experimental acute pancreatitis in rats
Rats were done with abdominal operation after anesthesia of 3% pentobarbital sodium, and then infused slowly 3.5% sodium taurocholate 0.1mg/100g in cholangiopancreatic duct t, whereas control group were infused the same amount physiological saline. Rats were randomly divided into six groups: the blank group (NS group), the model group (ANP+NS group) and the high-dose elafin group, the medium-dose group, the low-dose group, the positive control group, with 10 rats in each group. In addition of tosodium taurocholate, the high,medium,low-dose elafin groups received intravenous infusion of (5IU/kg、10IU /kg、20IU/kg)elafin, while the control and model group received the same amount of physiological saline, with the period of every 8 hours one infusion , continuously 6 times . 48 hours after the last injection, the blood samples from the abdominal aorta were obtained, then the serum NO, SOD,LPO, content were detected; After the pancreatic tissue homogenate, the tissue protein, amylase, lipase, SOD,LPO content were detected; pathological changes of rats pancreatic tissue were observed and its morphological structure were observed by electron microscope.
Test 1 Results
1 The changes of Amylase and Lipase of serum and pancreatic tissue: After treatment, serum and pancreatic tissue amylase and lipase in model group increased significantly(p<0.001), Compared with the model group,serum amylase and lipase of elafin(low dose, medium dose, high dose) groups decreased significantly (p<0.05, p<0.01 or p<0.001). The effect of high dose group is almost equal to aprotinin group.
2 The changes of SOD and LPO of serum and pancreatic tissue and the serum NO:
The serum and pancreatic tissue SOD in model group decreased significantly(p<0.001 ) . while the content of LPO and NO increased significantly(p<0.001). The serum and pancreatic tissue SOD in elafin(low dose, medium dose, high dose) groups increased significantly(p<0.001). while the content of LPO and NO decreased significantly(p<0.001). The effect of high dose group is almost equal to aprotinin group.
3 Morphological Changes of the Pancreatic Tissue;
In the model group, bloodyascites, necrotic foci in pancreas, and fat necrosis in mesentery and omentum was found grossly. Interstitial lobular inflammatory infiltrations were observed in pancreas microscopically, as well as diffusive bleeding and piecemeal necrosis. In elafin (low dose, medium dose, high dose) groups, ascites and fat necrosis diminished notably compared with those in the model group. Microscopically, slight bleeding, mild acinar degeneration and mild structure damage to lobules were observed together with declining inflammatory infiltration. The results show that the pathological changes significantly become light after elafin treatment.
4 The expression of TNF-α、NF-κB in Pancreatic Tissue In the model group, there are many positive cells which can express TNF-α、NF-κB in the pancreatic tissue, while few exists in the elafin (low dose, medium dose, high dose) groups.
Test 2 The effects of recombinant human elafin on experimental acute pancreatitis-associated lung injury in rats Rats were done with abdominal operation after anesthesia of 3% pentobarbital sodium, and then infused slowly 3.5% sodium taurocholate 0.1mg/100g in cholangiopancreatic duct t, whereas control group were infused the same amount physiological saline. Rats were randomly divided into six groups: the blank group (NS group), the model group (ANP+NS group) and the high-dose elafin group, the medium-dose group, the low-dose group, the positive control group, with 10 rats in each group. In addition of tosodium taurocholate, the high,medium,low-dose elafin groups received intravenous infusion of (2μg/kg、4μg /kg、8μg /kg)elafin, while the control and model group received the same amount of physiological saline, with the period of every 8 hours one infusion , continuously 6 times . 48 hours after the last injection, the lung W/D ratio was measured; the protein content of BALF was detected with Coomassie Breiliant Blue; after the lung tissue homogenate, the t TNF-α, MPO content were measured; pathological changes of rats lung tissue were observed and its morphological structure were observed by electron microscope.
Test 2 Results
1 The changes of lung W/D ratio and the protein of BALF Compared with the blank group, the lung W/D ratio and the protein of BALF in the model group increased significantly (p<0.001); Compared with the model group, the lung W/D ratio and the protein of BALF in the elafin (low dose, medium dose, high dose) groups decreased significantly(p<0.05, p<0.01 or p<0.001). The effect of high dose group is almost equal to aprotinin group.
2 The changes of TNF-α, MPO content in the lung tissue Compared with the blank group, the lung TNF-α, MPO content in the model group increased significantly (p<0.001); Compared with the model group, the lung TNF-α, MPO content in the elafin (medium dose, high dose) groups increased significantly(p<0.05, p<0.01). The effect of high dose group is almost equal to aprotinin group.
3 Morphological Changes of the Lung Tissue;
The blank group: the clear lung structure and the slim alveolar wall were observed; and there was no polymorph nuclear neutrophils infiltration. The model group: there were many neutrophils infiltration in the interstitial lung, especially around the vessel and little bronchus. The pulmonary edema became serious; part of the alveolus space was seen to be filled with effusion and neutrophils; alveolar septum significantly became broad. Compared with the model group, alveolar septum of the elafin (low dose, medium dose, high dose) groups significantly became slim; the infiltration of neutrophils significantly became less.
The above results show that elafin can significantly reduce serum amylase and lipase in AP group; inhibit the activation of pancreatic elastase and improve the hypersecretion in the pancreatitis. Elafin can reduce LPO of serum and pancreatic tissue rapidly and increase the SOD activity of serum and pancreatic tissue in acute pancreatitis, this suggests that elafin can improve its antioxidant activity by inhibiting lipid peroxide. Elafin can significantly inhibit the release of serum NO and prevent the interaction between inflammatory mediators and leukocytes, thus alleviate the development of acute pancreatitis. In the meantime, elafin can significantly reduce the lung W/D ratio and the protein of BALF and the lung TNF-α, MPO content in the pancreatitis-associated lung injury. According to the pathological observation, elafin can significantly reduce the edema, hemorrhage, and necrosis of pancreatic tissue, this suggest that it has the function of improving the organism repair capacity and protecting organs. Elafin can significantly reduce the infiltration of inflammatory cells in the lung and make the alveolar wall slim.
In conclusion, elafin can prevent and cure the acute pancreatitis and the acute pancreatitis-associated lung injury.
引文
1. McBride J D,Freeman H M,Leatherbarrow R J. Selection of human elastase inhibitors from a conformationally constrained combinatorial peptide library[J]. Eur J Biochem, 1999, 266(2): 403-412.
2. 张伟,蔡映云. 中性粒细胞弹性蛋白酶与炎症性肺部疾病[J]. 国外医学呼吸系统分册, 2002, 22(4): 171-174.
3. Yamashita J , Tashiro K , Yoneda S. Local increase in poly- morphonuclear leukocyte elastase is associated with tumorinvasiveness in non-small cell lung cance[J]. Chest, 1996, 109: 1328-1334.
4. Nozawa F,Hirota M,Okabe A. Elastase activity enhancesthe adhesion of neutrophil and cancer cells to vascularendothelial cells[J]. J Surg Res, 2000, 94(2): 153-158.
5. Lee W L,Downey G P. Leukocyte elastase physiological functions and role in acute lung injury[J]. Am J Respir CritCare Med,2001,164(5):896-904.
6. Kapui Z , Varga M , Urban-Szabó K. Biochemical and pharmacological characterization of 2-(9-(2-piperidinoethoxy)-4-oxo-4H-p[1,2-a] pyrimidin-2-yloxymethyl)-4-methylethyl)-6-methoxy-1,
2-benzisothiazol- 3(2H)-one-1,1-dioxide(SSR69071),a novel,orally active elastase inhibitor[J]. J Pharmacol Exp Ther,2003, 305(2): 451-459.
7. Shapiro SD. Neutrophil elastase, path clearer, pathogen killer,or just pathologic[J]. AmJ Respir Cell Mol Biof, 2002, 26(3): 266-268.
8. Houston DS, Carson W, Esmon CT, et al. Endothelial cells and extracellularc almodulini nhibitm onocytetu mornecrosis factor release and augment neutrophil elastase releas[J]. J Biol Chem, 1997, 272: 11778-11785.
9. Rainger GE, Rowley AF, Nash GB. Adhesion-dependent release of elastase from human neutrophilin novel flow -based model;specificity of different c hemotactic agents[J]. Blood, 1998, 92: 4819-4827.
10. Sue AK, Fialkow L, Valhos CJ, et al. Inhibition by neutrophil oxidative burst and granule secretion by wort-mannin; potential role of MAP kinase and renaturable kinases[J]. J Cell Physiol, 1997, 172: 94-108.
11. FrankE l, Elaine Sloand, LoriMain waring, et al. Clonaldominanc ofchronic myologenous leukemiais associated with diminished sensitivity to the antiproliferative effects of neutrophile lastase[J]. Blood, 2003, 102: 3786-3792.
12. El Ouriaghli F, Fujiwara H,Melenhorst JJ, et al. Neutrophil elastase nzymatically atagonizesthe in vitro action of G-CSF, implications forth eregulation of granulopoiesis[J]. Blood, 2003, 101: 1752-1758.
13. Ginzberg H, Dong Q, Cantin A, et al. Neutrophil mediated epithelial injury during transmigration role of elastase[J]. Am J Physiol, 2003, 281: 705- 725.
14. Yong RE, Thompson RD, Larbi KY,et al.Neutrophilelastase-deficient mice demonstrate a nonredundant role for NE in neutrophil migration ,generation of proinflammatory mediators, and phagocytosis in response to zymo-san particles in vivo[J]. Immunol, 2004, 172(7): 4493-4502.
15. Hirche T0, Atkinson JJ, Bahr S, et al. Deficiency in neutrophil elastase does not impair neutrophil recruitment to imflamed sites[J]. Am J Respir Cell Mol Biol, 2004, 30(4): 576-584.
16. Belaaouaj A, Mc Carthy R, Baumann M, et al. lacking against neutrophil elastase reveal impaired host Mice defens gram negative bacterial sepsis[J]. Nat Med, 1998, 4(5): 615-618.
17. Tkalcevic J, Novelli M, Phylactides M, et al. Impaired immunity and enhanced resistance to endotoxin in the absence of neutrophil elastase and cathepsin G[J]. Immunity, 2000, 12(2): 201-210.
18. Belaaouaj A, Kim KS, Shapiro SD. Degradation of outer membrane protein A in Escherichia coli killing by neutrophil elastase[J]. Science, 2000, 289(5482): 1185-1188.
19. Weinrauch Y, Drujan D, Shapiro SD, et al. Neutrophil elastase targets virulence factors of enterobacteria[J]. Nature, 2002, 417(2): 91-94.
20. Lopez-Boado YS, Espinola M,Bahr S, et al. Neutro-phil serine proteinases cleave bacterial flagellin, abroga-ting its host response-inducing activity[J]. J Immunol, 2004, 172(1): 509-515.
21. Owen CA, Campbell MA, Boukedes SS, et al. Cytokines regulate membrane-bound leukocyte elastase on neutrophils: a novel mechanism for effector activity[J]. Am J Physiol, 1997, 272(3): 385-393.
22. Cai TQ, Wright SD. Human leukocyte elastase is an endogenous ligand for integrin CR3 and modulates polymorphonu clear leukocyte adhesion[J]. J Exp Med, 1996, 184(4): 1213-1223.
23. Dimartirlo SJ, Shah AB, Trujillo G, et al. Elastase controls the binding of Vitamine D–binding protein to neurophils: a potenial role of in theregulation of C 5a co-chemtacticactivity[J]. J Immunol, 2001, 166(4): 2688-2694.
24. Carden D, Xiao F, Moak C, et al. Neurophil elastase promotes lung Mico- vascular injury and proteolysis of endothelial cadherins[J]. Am J Physiol, 1998, 275(2): 385-392.
25. Moraes TJ, Chow CW, Downey GP, Proteases and lung injury[J]. Crit Care Med, 2003, 31(4): S189-S192.
26. Warren LL, Gregory PD. Leukocyte elastase: physiological functions functions and role in acute lung injury[J]. Am J Respir Crit Care Med, 2001, 164(5): 896-904.
27. 侯继锋. 用离子交换层析法提纯人血浆组分IV21 中的α1 蛋白酶抑制剂[J]. 国外医学生物制品分册, 1999, 22(2): 91-92.
28. Senra AV, Bosco JJ, Lopez S. Utility of plasmatic levels of Alpha-1 antiprotease(A1AP) as a cancer marker[J]. Cancer Letters, 1995, 89 (1): 15-21.
29. Perlmutter D H.α1-antitrypsin deficiency:diagnosis and treatmen[J]. Clin Liver Dis, 2004, (84): 839-859.
30. Im H, Seo EJ, Yu M. Metastability in the inhibitory mechanism of humanα1-antitrypsin[J]. J Biol Chem, 1999, 274(16): 11072-11077.
31. Clark R A,Stone P J,Hag A E. Myeloperoxidase-catalyzed inactivation of αl-protease inhibitor by human neutrophils[J]. J Biol Chem, 1981, 256(7): 3348-3353.
32. Remold-O’Donnell E , Nixon JC , Rose RM. Elastase inhibitor characterization of the human elastase inhibitor molecule associated with monocytes, macrophages, and neutrophils[J]. J Exp Med, 1989, 169(3): 1071-1086.
33. Celine F, Manuel D, Alain A, et al. Solution structure of R-elafin, a specific inhibitor of elastase[J]. J Mol Biol, 1997, 268(11): 666-677.
34. Michele W, Michele P, Norman S. Inhibition of human mast cell chymase by secretory leukocyte proteinase inhibitor: enhancement of the interaction by heprin[J]. Achieves Biochem Biophys, 1996, 327(1): 81-88.
35. Simpson AJ, Maxwell AJ, Haslett C, et al. Elafin has anti-microbial activity against Gram-positive and Gram-negative respiratory pathogens[J]. Federa Eur Biochem Soc, 1999, 452(3): 309-313.
36. Pemberton AD, Huntley JF, Miller HRP. Differential inhibition of mast cell chymase by secretory leukocyte protease inhibitor[J]. Biochem Biophys Acta, 1998, 1379(1): 29-34.
37. Anne EK, Kevin M, Sallenare JM, et al. Differential regulation of secretory leukocyte protease inhibitor and elafin by progesterone[J]. Biochem Biophys Res Communi, 2003, 310(2): 594-599.
38. Reid PT, Marsden ME, Cunninghain GA, et al. Human neutrophil elastase regulates the expression and secretion of elafin in type Ⅱ alveolar epit helial cells[J]. Federa Eur Biochem Soc, 1999, 457(1): 33-37.
39. Yoshihiko S, Nobutaka L, Hiroshi A, et al. Expression of tissue trausglutaminase and elafin in human coronary: implication for plaque instability[J]. At herosclerosis, 2002, 160(1): 31-39.
40. Naoya Y, Hiroshi E, Hidenobu K, et al. Immunohistochemical expression of SKALP/elafin in squamous cellcarcinoma of human lung and esophagus[J]. Int Congress Series, 2003, 1255(5): 299-303.
41. Tremblay G M,Vachon E,Larouche C. Inhibition of human neutrophil elastase -induced acute lung injury in hamsters by recombinant human pre-elafin (trappin-2) [J]. Chest, 2002, 121(2): 582-588.
42. Cowan B,Baron O,Crack J. Elafin,a serine elastase inhibitor,attenuates post-cardiac transplant coronary arteriopathy and reduces myocardial necrosis in rabbits after heterotopic cadiac transplantation[J]. J Clin Invest, 1996, 97(11): 2452-2468.
43. Cowan K N,Jones P L, Rabinovitch M. Elastase and matrix Metallo proteinase inhibitors induce regression , and tenascin-C antisense prevents progression,of vascular disease[J]. J Clin Invest, 2000, 105(1): 21-34.
44. O’Blenes S B,Zaidi S H,Cheah A Y. Gene transfer of the serine elastase inhibitor elafin protects against vein graft degeneration[J]. Circulation, 2000, 102(19): 289-295.
45. 汤国梅.α2-巨球蛋白基因与Alzheimer病的研究进展[J]. 国外医学精神病学分册, 2002, 29(1): 56-59.
46. 杜冠华,吴松,冯文化. 西维来司钠治疗急性肺损伤研究现状[J]. 中国药学杂志, 2004, 39(5): 321-324.
47. Kang K,Bae S J,Kim W M. Molecular characteristics of the inhibition of human neutrophil elastase by nonsteroidal anti inflammatory drugs[J]. Exp Mol Med, 2000, 32(3): 146-154.
48. Taylor P,Anderson V,Dowden J. Novel mechanism of inhibition of elastase by β-lactams is defined by two inhibitor crystal complexes[J]. J Biol Chem, 1999, 274(35): 24901-24905.
49. Tsunemi M,Kato H ,Nishiuchi Y. Synthesis and structure activity relationships of elafin,an elastase-specific inhibitor[J]. BiochemBiophys Res Commun, 1992, 185(3): 967-973.
50. McBride J D,Freeman H M,Leatherbarrow R J. Selection of human elastase inhibitors from a conformationally constrained combinatorial peptide library[J]. Eur J Biochem, 1999, 266(2): 403-412.
51. Zani ML, Nobar SM, Lacour SA, Lemoine S, Boudier C, Bieth JG, Moreau T. Kinetics of the inhibition of neutrophil proteinases by recombinant elafin and pre-elafin (trappin-2) expressed in Pichia pastoris[J]. Eur J Biochem, 2004, 271(12): 2370-2378.
52. Molhuizen HO, Schalkwijk J. Structural, biochemical, and cell biological aspects of the serine proteinase inhibitor SKALP/elafin/ESI[J]. Biol Chem Hoppe Seyler, 1995, 376(1): 1-7.
53. Sallenave JM, Silva A, Marsden ME, Ryle AP. Secretion of mucus proteinase inhibitor and elafin by Clara cell and type II pneumocyte cell lines[J]. Am J Respir Cell Mol Biol, 1993, 8(2): 126-33.
54. Yuji Higashimoto, Yuko Yamagata, Takuya Iwata et al. Adenoviral E1A Suppresses Secretory Leukoprotease Inhibitor and Elafin Secretion in Human Alveolar Epithelial Cells and Bronchial Epithelial Cells[J]. Basic Science Investigations, 2005, 72: 629–635.
55. Saheki T, Ito F, Hagiwara H, et al. Primary structure of the human elafin precursor preproelafin deduced from the nucleotide sequence of its gene and the presence of unique repetitive sequences in the prosegment[J]. Biochem Biophys Res Commun, 1992, 185(1): 240-245.
56. Zhang M, Zou Z, Maass N, et al. Differential expression of elafin in human normal mammary epithelial cells and carcinomas is regulated at the transcriptional level[J]. Cancer Res, 1995, 55(12): 2537-2541.
57. Tamechika I, Itakura M, Saruta Y, et al. Accelerated evolution in inhibitor domains of porcine elafin family members[J]. J Biol Chem, 1996, 271(12): 7012-7018.
58. Robinson PA, Leek JP, Carr IM, e al. Yeast artificial chromosome cloning and chromosomal localization of the abundant odontogenic keratocyst protein elafin[J]. Arch Oral Biol, 1996, 41(5): 445-452.
59. Lundwall A, Ulvsback M. The gene of the protease inhibitor SKALP/elafin is a member of the REST gene family[J]. Biochem Biophys Res Commun, 1996, 221(2): 323-327.
60. Pol A, Pfundt R, Zeeuwen P, et al. Transcriptional regulation of the elafin gene in human keratinocytes[J]. J Invest Dermatol, 2003, 120(2): 301-307.
61. Molhuizen HO, Alkemade HA, Zeeuwen PL, et al.SKALP/elafin: an elastaseinhibitor from cultured human keratinocytes. Purification, cDNA sequence, and evidence for trans glutaminase cross-linking[J]. J Biol Chem, 1993, 268(16): 12028-12032.
62. Van Bergen BH, Andriessen MP, Spruijt KI, et al. Expression of SKALP/elafin during wound healing in human skin[J]. Arch Dermatol Res, 1996, 288(8): 458-462.
63. Nara K, Ito S, Ito T, et al. Elastase inhibitor elafin is a new type of proteinase inhibitor which has a transglutaminase-mediated anchoring sequence termed cementoin[J]. J Biochem, 1994, 115(3): 441-448.
64. Francart C, Dauchez M, Alix AJ, et al. Solution structure of R-elafin, a specific inhibitor of elastase[J]. J Mol Biol, 1997, 268(3): 666-677.
65. Tsunemi M, Kato H, Nishiuchi Y, et al. Synthesis and structure[J]. Biochem Biophys Res Commun, 1992, 185(3): 967-73.
66. Ying QL, Simon SR. Kinetics of the inhibition of proteinase 3 by elafin[J]. Am J Respir Cell Mol Biol, 2001, 24(1): 83-89.
67. Fitch PM, Roghanian A, Howie SE, et al. Human neutrophil elastase inhibitors in innate and adaptive immunity[J]. Biochem Soc Trans, 2006, 34(2): 279-282.
68. Vandermeeren M, Daneels G, Bergers M, et al. Development and application of monoclonal antibodies against SKALP/elafin and other trappin family members[J]. J Immunol, 2001, 293(7): 343-349.
69. Ying QL, Simon SR. Kinetics of the inhibition of human leukocyte elastase by elafin, a 6-kilodalton elastase-specific inhibitor from human skin[J]. Biochemistry, 1993, 32(7): 1866-1874.
70. Henrik sen PA , H ittM , Xing Z, et al. A denoviral gene delivery of elafin and secretory leukocyte protease inhibitor attenuates NF-kappaB- dependent-inflammatory responses of human endothelialcells and macrophages to atherogenic stimuli[J]. J Immunol, 2004, 172(7): 4535- 4544.
71. V achon E, Bourbonnais Y, Bingle CD, et al. Anti-inflammatory effect of pre-elafin in lipopo lysaccharide-induced acute lung inflammation[J]. Biol Chem, 2002, 383(728): 1249-1256.
72. MulliganM S, Lentsch AB, Huber-Lang M, et al. Anti-inflammatory effects of mutant forms of secretory leukocyte protease in-hibitor[J]. Am J Pathol, 2000, 156(3): 1033-1039.
73. Hiemstal PS, Maassen RJ, Stolk J. Antibacterial activity of antileukoprotease[J]. Infect Immun, 1996, 64(11): 4520-4524.
74. Sallenave JM, Cunningham GA, James RM, et al. Regulation ofpulmonary and systemic bacterial lipopolysaccharide responses intransgenic mice expressing human elafin[J]. Infect Immun, 2003, 71(7): 3766-3774.
75. 张英. 重组人在毕氏酵母中表达鉴定及大规模发酵和纯化工艺研究. 2006年
76. 黄洁夫, 主编. 腹部外科学[M]. 北京人民卫生出版社, 2001: 1476-1482.
77. Janowitz P, Von Moltke A, Weidmann B. Acute pancreatitis caused by atrial fibrillation[J]. Dtsch Med ochenschr, 2002, 127(50): 2669-72.
78. Olson EL, Whang YE. Hypertriglyceridemia and pancreatitis associated with estramustine phosphate[J]. Am J Clin Oncol, 2002, 25: 342-343.
79. Artac M, Sari R, Altunbas H, et al. Asymptomatic acute pancreatitis due to tam oxifeninduced severe hypertriglyceridemia in a patient with diabetesmellitus and breast cancer[J]. J Chemother, 2002, 14: 309-311.
80. Martinez J, Sanchez-Paya J, Palazon JM, et al. Is obesity a risk factor inacute pancreatitis[J]. Ameta–analysis. Pancreatology, 2004, 4(1):42- 48.
81. Linder JD, Geels W, Wilcox CM. Prevalence of sphincter of Oddi dysfunction: can results from specialized centers be generalized[J]. Dig Dis Sci, 2002, 47: 2411-2415.
82. Coyle WJ, Pineau BC, Tarnasky PR, et al. Evaluation of unexplained acuteand acute recurrent pancreatitis using endoscopic retrogiade cholangiopan- creatography, sphincter of Oddi manometry and endoscopic ultrasound[J]. Endoscopy, 2002, 34: 617-623.
83. Gislason H, Horn A, Hoem D, et al. Acute pancreatitis in Bergen, Norway: A study on incidence, etiology and severity[J]. Scand J Surg, 2004, 93(1): 29-33.
84. Battillocchi B, Diana M, Dandolo R, et al. Drug-induced acute pancreatitis: a personal contribution[J]. Chir Ital, 2002, 54: 605-612.
85. Onosaka S, Tetsuchikawahara N, Min KS. Paradigm shift in zinc: metalpathology[J]. Tohoku J Exp Med, 2002, 196:1-7.
86. Hassan I, Zietlow SP. Acute pancreatitis after extracorporeal shock wavelithotripsy for a renal calculus[J]. Urology, 2002, 60: 111-124.
87. Elias D, Baton O, Sideris L, et al. Necrotizing pancreatitis after radiofre-quency destruction of pancreatic tumours[J]. Eur J Surg Oncol, 2004, 30(1): 85-87.
88. Esmer Sanchez D, Rangel D. Inflammatory pseudotumor of the retrope- ritioneum[J]. Rev Gastroenterol Mex, 2002, 67: 97-99.
89. Pascual-Ramos V, Duarte-Rojo A, Villa AR, et al. Systemic lupusery thematosus as a cause and prognostic factor of acute pancreatitis[J]. J Rheumatol, 2004, 31(4): 707-712.
90. Sanchez-Lozada RA, Costa-Rosero AV, Chapa-Azuela O, et al. Etiology on determining the severity of acute pancreatitis[J]. Gac Med Mex, 2003, 139 (1): 27-31.
91. Gullo L, Migliori M, Olah A, et al. Acute pancreatitis in five European countries∶etiology and mortality[J]. Pancreas, 2002, 24(3): 223-227.
92. 陈浩, 李非, 程韵枫, 等. 大鼠重症急性胰腺炎病情演变中中性白细胞的作用[J]. 世界华人消化杂志, 2001, 9(7): 776–779.
93. 谭至柔, 唐国都, 姜海行, 等. 抗氧化剂对急性胰腺炎大鼠核因子-KB和一氧化氮合酶的影响[J]. 世界华人消化杂志, 2004, 12(3): 711–713.
94. 张晓华, 李兆申, 屠振兴, 等. Caspase-1激活的细胞因子在实验性重症急性胰腺炎肺损伤中的作用[J]. 解放军医杂志, 2003, 28(12): 1074-1076.
95. 彭晓辉, 于剑波, 高宏凯, 等. 急性胰腺炎胰腺内源性RAS的活化与局部微循环P选择素表达变化规律的研究[J]. 华西医学, 2003, 18(4): 465-466.
96. Nagar AB, Go relick FS. A cute pancreatitis[J]. Curr Op in Gastroenterol, 2004, 20: 439-443.
97. Dominguez-Munoz JE, Effer B, Sauerbruch T, et al. Dynamics and factors related with the ERCP-induced elevation of serum pancreatic enzymes[J]. Digestion, 1995, 56: 290.
98. Jaffray C, Yang J, Carter G, et al. Pancreatic elastase activates pulmonary nuclear factor kappa B and inhibitory kappa B, mimicking pancreatitis-associated adult respiratory distress syndrome[J]. Surgery, 2000, 128(2): 225-231.
99. Werner J, Dragotakes SC, Fernandez-del Castillo C, et al. Technetium 299m- labeled white blood cells: a new method to define the local and systemic role of leukocytes in acute experimental pancre-atitis [J]. Ann Surg, 1998, 227(1): 86-94.
100.Bhatia M, Saluja AK, HofbauerB, et al. The effects of neutrophil depletion on a completely noninvasive model of acute pancreatitis-associated lung injury[J]. Int J Pancreatol, 1998, 24(2): 77-83.
101.Hartwig W, Werner J, Warshaw AL, et al. Membrane-bound ICAM-1 is up regulated by trypsin and contributes to leukocyte mi-gration in acute pancreatitis[J]. Am J Physiol Gastrointest Liver Physiol, 2004, 287(6): G11942-G1199.
102.Hartwig W, Carter EA, Jimenez RE, et al. Neutrophil metabolic activity but not neutrophil sequestration reflects the development of pancreatitis associated lung injury[J]. Crit CareMed, 2002, 30(9): 2075-2082.
103.Pereda J, Sabater L, Cassinello N, Gomez-Cambronero L, et al. Effect of imultaneous inhibition of TNF-alpha production and xan-thine oxidase in experimental acute pancreatitis: the role of mito-gen activated protein kinases[J]. Ann Surg, 2004, 240(1): 108-116.
104.Minter RM, Ferry MA, Murday ME, et al. Adenoviral delivery of human and viral IL-10 in murine sepsis[J]. J Immunol, 2001, 167(2): 1053-1059.
105.Osman MO, Kristensen JU, Jacobsen NO, et al. A monoclonal Anti- interleukin 8 antibody (WS24) inhibits cytokine response andacute lung injury in experimental severe acute necrotising pancreas-titis in rabbits [J]. Gut, 1998, 43(2): 232-239.
106.Maa J, Grady EF, Yoshimi SK, et al. Substance P is a determi-nant of lethality in diet-induced hemorrhagic pancreatitis in mice[J]. Surgery, 2000, 128(2): 232-239.
107.Shi X, Gao NR, Yin Y, et al. Role of neurokinin-1 receptor in lung injury in rats with acute necrotizing pancreatitis[J]. Zhong-guo Wei Zhong Bing Ji Jiu Yi Xue, 2003, 15(7): 422-425.
108.Lau HY, Wong FL, BhatiaM. A key role of neurokinin 1 receptors in acute pancreatitis and associated lung injury [J]. Biochem Biophys Res Commun, 2005, 327(2): 509-515.
109.Gray KD, Simovic MO, Chapman WC, et al. Systemic NF-kappa B activation in a transgenic mouse model of acute pancreatitis[J]. J Surg Res, 2003, 110(1): 310-314.
110.Ware LB, Matthay MA. The acute respiratory distress syndrome[J]. N Engl J Med, 2000, 342(18): 1334-1349.
111.BhatnagrA, Wig JD, Majumdar S. Expression of activation,adhesion molecules and intracellular cytokines in acute pancreatitis[J]. Immunol Lett, 2001, 77: 133-141.
112.Grewl HP,KotbM, Mohy EI Din A, et al. Induion of tumor necrosis Factor in severe acute pancreatitis and its subsequent re-dution after hepatic passage[J]. Surgery, 1994, 115: 213-221.
113.史君, 李春跃, 杨桂花. 白细胞介素-6与心血管疾病[J]. 内蒙古医学院学报, 2004, 26(1): 66-68.
114.Yoshimura T, Matsushima K, Oppenheim JJ, et al. Neutrophil chemotactic factor produced by lipopolysaccharide (LPS) stimulated human bloodmononuclear leukocytes: partial characterization and separation from interleukin 1(IL-1)[J]. J Immunol, 1987, 139: 788-793.
115.BaggioliniM. Chemokines in pathology and medicine [J]. J Intern Med, 2001, 250: 91-104.
116.Benveniste J , Henson PM, Cochrane CG, et al. Leukocyte dependent histamine release from rabbit p latelets. The role of IgE, basophils, and a platelet- activating factor[J]. J Exp Med, 1972, 136: 1356-1377.
117.Curley P, Nestor M, Collins K, et al. Decreased Interleukin-2 Production in Murine Acrte Pancreatitis: Potential for Immunomodulation [J]. Gastroenterology, 1996, 110(2): 583-588.
118.金忱, 倪泉兴, 张群华, 等. 急性胰腺炎大鼠TNF-α和IL-10 mRNA的表达及其意义[J]. 外科理论与实践, 2001, 6(6): 379-382.
119.王先坤, 詹乐恒, 王世文, 等. IL-10、IL-18 在重症急性胰腺炎肺损伤中的作用[J]. 中国普外基础与临床杂志, 2005, 12(5): 443-446.
120.邓群, 黎沾良, 姚咏明, 等. 急性坏死性胰腺炎早期血清细胞因子的变化及免疫干扰的影响[J]. 中国危重病急救医学, 1999, 11(6): 358-360.
121.尤家禄. 缺血-再灌注损伤[A]. 见: 王迪浔, 金惠铭, 主编. 病理生理学[M]. 北京:人民卫生出版社, 1995. 323-336.
122.魏捷, 秦兴雷, 鲁敏, 等. 重症急性胰腺炎微循环障碍的实验研究[J]. 实用诊断与治疗杂志, 2003, 17(3): 180-182.
123.金惠铭, 主编. 病理生理学[M]. 第5版. 北京: 人民卫生出版社, 2002. 153-156.
124.Chang CK, Albarillo MV, Schumer W. Therapeutic effect of dimethyl sulfoxide on ICAM-1 gene expression and activation of NF-kappB and AP-1 in septic rats[J]. J Surg Res, 2001, 95: 181-187.
125.郭莲怡,金旭鹏,李舒. 参附注射液对重症急性胰腺炎患者血浆内皮素、一氧化氮浓度的影响[J]. 中国中医急诊, 2007, 16(3): 298-299.
126.Schmidt H, Creutzfeldt W. The possible role of phospholipase A in the pathogenesis of acute pancreatitis[J]. Scand J Gastroenterol, 1969, 4(1): 39-48.
127.Kihara Y, Yoshikawa H, Honda H, et al. Natural disrup tion ofgroup 2 phospholipase A2 gene protects against choline-deficientethionine -supplemented diet-induced acute pancreatitis and lunginjury[J]. Pancreas, 2005, 31(1): 48-53.
128.Jaffray C, Yang J, Carter G, et al. Pancreatic elastase activates pulmonary nuclear factor kappa B and inhibitory kappa B, mimicking pancreatitis- associated adult respiratory distress syndrome[J].Surgery, 2000, 128(2): 225-231.
129.HartwigW, Carter EA, J imenez RE, et al. Neutrophil metabolic activity but not neutrophil sequestration reflects the development of pancreatitis -associated lung injury [J]. Crit CareMed, 2002, 30(9): 2075-2082.
130.张刚,张肇达, 等. 实验性急性胰腺炎大鼠肺内肿瘤坏死因子mRNA的表达及其意义[J]. 华西医科大学学报,1999, 30: 379-381.
131.Frossard JL, Saluja A, Bhagat L. The role of intercellular adhesion molecular 1 and neutrophils in acute pancreatits and pancreatits -associated lung injury[J]. Gastroenterology, 1999, 116: 694-701.
132.Tsukahara Y,Morisaki T,Horita Y.Role of nitric oxide derived from alveolar macrophages in the early phase of acute pancreatits[J]. J Surg Res, 1996, 66: 43-50.
133.Gray KD, Simovic MO, Chapman WC, et al. Systemic NF-kappaB activation in a transgenic mouse model of acute pancreatitis[J]. J Surg Res, 2003, 110(1): 310-314.
134.Ethridge RT, Hashimoto K, ChungDH, et al. Selective inhibition of NF- kappaB attenuates the severity of cerulean-induced acute pancreatitis [J]. J Am Coll Surg, 2002, 195(4): 497-505.
135.Frossard JL, Kwak B, Chanson M, et al. Cd40 ligand-deficient mice are protected against cerulean-induced acute ancreatitis and pancreatitis -associated lung injury[J]. Gastroenterology, 2001, 121(1): 184-194.
136.Ware LB, Matthay MA. The acute respiratory distress syndrome [J]. N Engl J Med, 2000, 342(18): 1334-1349.
137.Reid PT, Marsden ME, Cunninghain GA, et al. Human neutrophil elastase regulates t he expression and secretion of Elafin in type Ⅱ alveolar epit helial cells[J]. Federa Eur Biochem Soc, 1999, 457(1): 33-37.
138.Anne EK, Kevin M , Sallenare JM,et al. Differential regulation of secretory leukocyte protease inhibitor and elafin by progesterone[J]. Biochem Biophys Res Communi, 2003, 310(2): 594-599.
139.Yoshihiko S, Nobutaka L, Hiroshi A, et al. Expression of tissue trans glutaminase and elafin in human coronary: implication for plaque instability[J]. At herosclerosis, 2002, 160(1): 31-39.
140.Naoya Y, Hiroshi E , Hidenobu K, et al . Immunohistochemical expression of SKALP/ elafin in squamous cell carcinoma of human lung and esophagus. Int Congress Series ,2003 ,1255 (5) :299-303.
2. 张伟,蔡映云. 中性粒细胞弹性蛋白酶与炎症性肺部疾病[J]. 国外医学呼吸系统分册, 2002, 22(4): 171-174.
3. Yamashita J , Tashiro K , Yoneda S. Local increase in poly- morphonuclear leukocyte elastase is associated with tumorinvasiveness in non-small cell lung cance[J]. Chest, 1996, 109: 1328-1334.
4. Nozawa F,Hirota M,Okabe A. Elastase activity enhancesthe adhesion of neutrophil and cancer cells to vascularendothelial cells[J]. J Surg Res, 2000, 94(2): 153-158.
5. Lee W L,Downey G P. Leukocyte elastase physiological functions and role in acute lung injury[J]. Am J Respir CritCare Med,2001,164(5):896-904.
6. Kapui Z , Varga M , Urban-Szabó K. Biochemical and pharmacological characterization of 2-(9-(2-piperidinoethoxy)-4-oxo-4H-p[1,2-a] pyrimidin-2-yloxymethyl)-4-methylethyl)-6-methoxy-1,
2-benzisothiazol- 3(2H)-one-1,1-dioxide(SSR69071),a novel,orally active elastase inhibitor[J]. J Pharmacol Exp Ther,2003, 305(2): 451-459.
7. Shapiro SD. Neutrophil elastase, path clearer, pathogen killer,or just pathologic[J]. AmJ Respir Cell Mol Biof, 2002, 26(3): 266-268.
8. Houston DS, Carson W, Esmon CT, et al. Endothelial cells and extracellularc almodulini nhibitm onocytetu mornecrosis factor release and augment neutrophil elastase releas[J]. J Biol Chem, 1997, 272: 11778-11785.
9. Rainger GE, Rowley AF, Nash GB. Adhesion-dependent release of elastase from human neutrophilin novel flow -based model;specificity of different c hemotactic agents[J]. Blood, 1998, 92: 4819-4827.
10. Sue AK, Fialkow L, Valhos CJ, et al. Inhibition by neutrophil oxidative burst and granule secretion by wort-mannin; potential role of MAP kinase and renaturable kinases[J]. J Cell Physiol, 1997, 172: 94-108.
11. FrankE l, Elaine Sloand, LoriMain waring, et al. Clonaldominanc ofchronic myologenous leukemiais associated with diminished sensitivity to the antiproliferative effects of neutrophile lastase[J]. Blood, 2003, 102: 3786-3792.
12. El Ouriaghli F, Fujiwara H,Melenhorst JJ, et al. Neutrophil elastase nzymatically atagonizesthe in vitro action of G-CSF, implications forth eregulation of granulopoiesis[J]. Blood, 2003, 101: 1752-1758.
13. Ginzberg H, Dong Q, Cantin A, et al. Neutrophil mediated epithelial injury during transmigration role of elastase[J]. Am J Physiol, 2003, 281: 705- 725.
14. Yong RE, Thompson RD, Larbi KY,et al.Neutrophilelastase-deficient mice demonstrate a nonredundant role for NE in neutrophil migration ,generation of proinflammatory mediators, and phagocytosis in response to zymo-san particles in vivo[J]. Immunol, 2004, 172(7): 4493-4502.
15. Hirche T0, Atkinson JJ, Bahr S, et al. Deficiency in neutrophil elastase does not impair neutrophil recruitment to imflamed sites[J]. Am J Respir Cell Mol Biol, 2004, 30(4): 576-584.
16. Belaaouaj A, Mc Carthy R, Baumann M, et al. lacking against neutrophil elastase reveal impaired host Mice defens gram negative bacterial sepsis[J]. Nat Med, 1998, 4(5): 615-618.
17. Tkalcevic J, Novelli M, Phylactides M, et al. Impaired immunity and enhanced resistance to endotoxin in the absence of neutrophil elastase and cathepsin G[J]. Immunity, 2000, 12(2): 201-210.
18. Belaaouaj A, Kim KS, Shapiro SD. Degradation of outer membrane protein A in Escherichia coli killing by neutrophil elastase[J]. Science, 2000, 289(5482): 1185-1188.
19. Weinrauch Y, Drujan D, Shapiro SD, et al. Neutrophil elastase targets virulence factors of enterobacteria[J]. Nature, 2002, 417(2): 91-94.
20. Lopez-Boado YS, Espinola M,Bahr S, et al. Neutro-phil serine proteinases cleave bacterial flagellin, abroga-ting its host response-inducing activity[J]. J Immunol, 2004, 172(1): 509-515.
21. Owen CA, Campbell MA, Boukedes SS, et al. Cytokines regulate membrane-bound leukocyte elastase on neutrophils: a novel mechanism for effector activity[J]. Am J Physiol, 1997, 272(3): 385-393.
22. Cai TQ, Wright SD. Human leukocyte elastase is an endogenous ligand for integrin CR3 and modulates polymorphonu clear leukocyte adhesion[J]. J Exp Med, 1996, 184(4): 1213-1223.
23. Dimartirlo SJ, Shah AB, Trujillo G, et al. Elastase controls the binding of Vitamine D–binding protein to neurophils: a potenial role of in theregulation of C 5a co-chemtacticactivity[J]. J Immunol, 2001, 166(4): 2688-2694.
24. Carden D, Xiao F, Moak C, et al. Neurophil elastase promotes lung Mico- vascular injury and proteolysis of endothelial cadherins[J]. Am J Physiol, 1998, 275(2): 385-392.
25. Moraes TJ, Chow CW, Downey GP, Proteases and lung injury[J]. Crit Care Med, 2003, 31(4): S189-S192.
26. Warren LL, Gregory PD. Leukocyte elastase: physiological functions functions and role in acute lung injury[J]. Am J Respir Crit Care Med, 2001, 164(5): 896-904.
27. 侯继锋. 用离子交换层析法提纯人血浆组分IV21 中的α1 蛋白酶抑制剂[J]. 国外医学生物制品分册, 1999, 22(2): 91-92.
28. Senra AV, Bosco JJ, Lopez S. Utility of plasmatic levels of Alpha-1 antiprotease(A1AP) as a cancer marker[J]. Cancer Letters, 1995, 89 (1): 15-21.
29. Perlmutter D H.α1-antitrypsin deficiency:diagnosis and treatmen[J]. Clin Liver Dis, 2004, (84): 839-859.
30. Im H, Seo EJ, Yu M. Metastability in the inhibitory mechanism of humanα1-antitrypsin[J]. J Biol Chem, 1999, 274(16): 11072-11077.
31. Clark R A,Stone P J,Hag A E. Myeloperoxidase-catalyzed inactivation of αl-protease inhibitor by human neutrophils[J]. J Biol Chem, 1981, 256(7): 3348-3353.
32. Remold-O’Donnell E , Nixon JC , Rose RM. Elastase inhibitor characterization of the human elastase inhibitor molecule associated with monocytes, macrophages, and neutrophils[J]. J Exp Med, 1989, 169(3): 1071-1086.
33. Celine F, Manuel D, Alain A, et al. Solution structure of R-elafin, a specific inhibitor of elastase[J]. J Mol Biol, 1997, 268(11): 666-677.
34. Michele W, Michele P, Norman S. Inhibition of human mast cell chymase by secretory leukocyte proteinase inhibitor: enhancement of the interaction by heprin[J]. Achieves Biochem Biophys, 1996, 327(1): 81-88.
35. Simpson AJ, Maxwell AJ, Haslett C, et al. Elafin has anti-microbial activity against Gram-positive and Gram-negative respiratory pathogens[J]. Federa Eur Biochem Soc, 1999, 452(3): 309-313.
36. Pemberton AD, Huntley JF, Miller HRP. Differential inhibition of mast cell chymase by secretory leukocyte protease inhibitor[J]. Biochem Biophys Acta, 1998, 1379(1): 29-34.
37. Anne EK, Kevin M, Sallenare JM, et al. Differential regulation of secretory leukocyte protease inhibitor and elafin by progesterone[J]. Biochem Biophys Res Communi, 2003, 310(2): 594-599.
38. Reid PT, Marsden ME, Cunninghain GA, et al. Human neutrophil elastase regulates the expression and secretion of elafin in type Ⅱ alveolar epit helial cells[J]. Federa Eur Biochem Soc, 1999, 457(1): 33-37.
39. Yoshihiko S, Nobutaka L, Hiroshi A, et al. Expression of tissue trausglutaminase and elafin in human coronary: implication for plaque instability[J]. At herosclerosis, 2002, 160(1): 31-39.
40. Naoya Y, Hiroshi E, Hidenobu K, et al. Immunohistochemical expression of SKALP/elafin in squamous cellcarcinoma of human lung and esophagus[J]. Int Congress Series, 2003, 1255(5): 299-303.
41. Tremblay G M,Vachon E,Larouche C. Inhibition of human neutrophil elastase -induced acute lung injury in hamsters by recombinant human pre-elafin (trappin-2) [J]. Chest, 2002, 121(2): 582-588.
42. Cowan B,Baron O,Crack J. Elafin,a serine elastase inhibitor,attenuates post-cardiac transplant coronary arteriopathy and reduces myocardial necrosis in rabbits after heterotopic cadiac transplantation[J]. J Clin Invest, 1996, 97(11): 2452-2468.
43. Cowan K N,Jones P L, Rabinovitch M. Elastase and matrix Metallo proteinase inhibitors induce regression , and tenascin-C antisense prevents progression,of vascular disease[J]. J Clin Invest, 2000, 105(1): 21-34.
44. O’Blenes S B,Zaidi S H,Cheah A Y. Gene transfer of the serine elastase inhibitor elafin protects against vein graft degeneration[J]. Circulation, 2000, 102(19): 289-295.
45. 汤国梅.α2-巨球蛋白基因与Alzheimer病的研究进展[J]. 国外医学精神病学分册, 2002, 29(1): 56-59.
46. 杜冠华,吴松,冯文化. 西维来司钠治疗急性肺损伤研究现状[J]. 中国药学杂志, 2004, 39(5): 321-324.
47. Kang K,Bae S J,Kim W M. Molecular characteristics of the inhibition of human neutrophil elastase by nonsteroidal anti inflammatory drugs[J]. Exp Mol Med, 2000, 32(3): 146-154.
48. Taylor P,Anderson V,Dowden J. Novel mechanism of inhibition of elastase by β-lactams is defined by two inhibitor crystal complexes[J]. J Biol Chem, 1999, 274(35): 24901-24905.
49. Tsunemi M,Kato H ,Nishiuchi Y. Synthesis and structure activity relationships of elafin,an elastase-specific inhibitor[J]. BiochemBiophys Res Commun, 1992, 185(3): 967-973.
50. McBride J D,Freeman H M,Leatherbarrow R J. Selection of human elastase inhibitors from a conformationally constrained combinatorial peptide library[J]. Eur J Biochem, 1999, 266(2): 403-412.
51. Zani ML, Nobar SM, Lacour SA, Lemoine S, Boudier C, Bieth JG, Moreau T. Kinetics of the inhibition of neutrophil proteinases by recombinant elafin and pre-elafin (trappin-2) expressed in Pichia pastoris[J]. Eur J Biochem, 2004, 271(12): 2370-2378.
52. Molhuizen HO, Schalkwijk J. Structural, biochemical, and cell biological aspects of the serine proteinase inhibitor SKALP/elafin/ESI[J]. Biol Chem Hoppe Seyler, 1995, 376(1): 1-7.
53. Sallenave JM, Silva A, Marsden ME, Ryle AP. Secretion of mucus proteinase inhibitor and elafin by Clara cell and type II pneumocyte cell lines[J]. Am J Respir Cell Mol Biol, 1993, 8(2): 126-33.
54. Yuji Higashimoto, Yuko Yamagata, Takuya Iwata et al. Adenoviral E1A Suppresses Secretory Leukoprotease Inhibitor and Elafin Secretion in Human Alveolar Epithelial Cells and Bronchial Epithelial Cells[J]. Basic Science Investigations, 2005, 72: 629–635.
55. Saheki T, Ito F, Hagiwara H, et al. Primary structure of the human elafin precursor preproelafin deduced from the nucleotide sequence of its gene and the presence of unique repetitive sequences in the prosegment[J]. Biochem Biophys Res Commun, 1992, 185(1): 240-245.
56. Zhang M, Zou Z, Maass N, et al. Differential expression of elafin in human normal mammary epithelial cells and carcinomas is regulated at the transcriptional level[J]. Cancer Res, 1995, 55(12): 2537-2541.
57. Tamechika I, Itakura M, Saruta Y, et al. Accelerated evolution in inhibitor domains of porcine elafin family members[J]. J Biol Chem, 1996, 271(12): 7012-7018.
58. Robinson PA, Leek JP, Carr IM, e al. Yeast artificial chromosome cloning and chromosomal localization of the abundant odontogenic keratocyst protein elafin[J]. Arch Oral Biol, 1996, 41(5): 445-452.
59. Lundwall A, Ulvsback M. The gene of the protease inhibitor SKALP/elafin is a member of the REST gene family[J]. Biochem Biophys Res Commun, 1996, 221(2): 323-327.
60. Pol A, Pfundt R, Zeeuwen P, et al. Transcriptional regulation of the elafin gene in human keratinocytes[J]. J Invest Dermatol, 2003, 120(2): 301-307.
61. Molhuizen HO, Alkemade HA, Zeeuwen PL, et al.SKALP/elafin: an elastaseinhibitor from cultured human keratinocytes. Purification, cDNA sequence, and evidence for trans glutaminase cross-linking[J]. J Biol Chem, 1993, 268(16): 12028-12032.
62. Van Bergen BH, Andriessen MP, Spruijt KI, et al. Expression of SKALP/elafin during wound healing in human skin[J]. Arch Dermatol Res, 1996, 288(8): 458-462.
63. Nara K, Ito S, Ito T, et al. Elastase inhibitor elafin is a new type of proteinase inhibitor which has a transglutaminase-mediated anchoring sequence termed cementoin[J]. J Biochem, 1994, 115(3): 441-448.
64. Francart C, Dauchez M, Alix AJ, et al. Solution structure of R-elafin, a specific inhibitor of elastase[J]. J Mol Biol, 1997, 268(3): 666-677.
65. Tsunemi M, Kato H, Nishiuchi Y, et al. Synthesis and structure[J]. Biochem Biophys Res Commun, 1992, 185(3): 967-73.
66. Ying QL, Simon SR. Kinetics of the inhibition of proteinase 3 by elafin[J]. Am J Respir Cell Mol Biol, 2001, 24(1): 83-89.
67. Fitch PM, Roghanian A, Howie SE, et al. Human neutrophil elastase inhibitors in innate and adaptive immunity[J]. Biochem Soc Trans, 2006, 34(2): 279-282.
68. Vandermeeren M, Daneels G, Bergers M, et al. Development and application of monoclonal antibodies against SKALP/elafin and other trappin family members[J]. J Immunol, 2001, 293(7): 343-349.
69. Ying QL, Simon SR. Kinetics of the inhibition of human leukocyte elastase by elafin, a 6-kilodalton elastase-specific inhibitor from human skin[J]. Biochemistry, 1993, 32(7): 1866-1874.
70. Henrik sen PA , H ittM , Xing Z, et al. A denoviral gene delivery of elafin and secretory leukocyte protease inhibitor attenuates NF-kappaB- dependent-inflammatory responses of human endothelialcells and macrophages to atherogenic stimuli[J]. J Immunol, 2004, 172(7): 4535- 4544.
71. V achon E, Bourbonnais Y, Bingle CD, et al. Anti-inflammatory effect of pre-elafin in lipopo lysaccharide-induced acute lung inflammation[J]. Biol Chem, 2002, 383(728): 1249-1256.
72. MulliganM S, Lentsch AB, Huber-Lang M, et al. Anti-inflammatory effects of mutant forms of secretory leukocyte protease in-hibitor[J]. Am J Pathol, 2000, 156(3): 1033-1039.
73. Hiemstal PS, Maassen RJ, Stolk J. Antibacterial activity of antileukoprotease[J]. Infect Immun, 1996, 64(11): 4520-4524.
74. Sallenave JM, Cunningham GA, James RM, et al. Regulation ofpulmonary and systemic bacterial lipopolysaccharide responses intransgenic mice expressing human elafin[J]. Infect Immun, 2003, 71(7): 3766-3774.
75. 张英. 重组人在毕氏酵母中表达鉴定及大规模发酵和纯化工艺研究. 2006年
76. 黄洁夫, 主编. 腹部外科学[M]. 北京人民卫生出版社, 2001: 1476-1482.
77. Janowitz P, Von Moltke A, Weidmann B. Acute pancreatitis caused by atrial fibrillation[J]. Dtsch Med ochenschr, 2002, 127(50): 2669-72.
78. Olson EL, Whang YE. Hypertriglyceridemia and pancreatitis associated with estramustine phosphate[J]. Am J Clin Oncol, 2002, 25: 342-343.
79. Artac M, Sari R, Altunbas H, et al. Asymptomatic acute pancreatitis due to tam oxifeninduced severe hypertriglyceridemia in a patient with diabetesmellitus and breast cancer[J]. J Chemother, 2002, 14: 309-311.
80. Martinez J, Sanchez-Paya J, Palazon JM, et al. Is obesity a risk factor inacute pancreatitis[J]. Ameta–analysis. Pancreatology, 2004, 4(1):42- 48.
81. Linder JD, Geels W, Wilcox CM. Prevalence of sphincter of Oddi dysfunction: can results from specialized centers be generalized[J]. Dig Dis Sci, 2002, 47: 2411-2415.
82. Coyle WJ, Pineau BC, Tarnasky PR, et al. Evaluation of unexplained acuteand acute recurrent pancreatitis using endoscopic retrogiade cholangiopan- creatography, sphincter of Oddi manometry and endoscopic ultrasound[J]. Endoscopy, 2002, 34: 617-623.
83. Gislason H, Horn A, Hoem D, et al. Acute pancreatitis in Bergen, Norway: A study on incidence, etiology and severity[J]. Scand J Surg, 2004, 93(1): 29-33.
84. Battillocchi B, Diana M, Dandolo R, et al. Drug-induced acute pancreatitis: a personal contribution[J]. Chir Ital, 2002, 54: 605-612.
85. Onosaka S, Tetsuchikawahara N, Min KS. Paradigm shift in zinc: metalpathology[J]. Tohoku J Exp Med, 2002, 196:1-7.
86. Hassan I, Zietlow SP. Acute pancreatitis after extracorporeal shock wavelithotripsy for a renal calculus[J]. Urology, 2002, 60: 111-124.
87. Elias D, Baton O, Sideris L, et al. Necrotizing pancreatitis after radiofre-quency destruction of pancreatic tumours[J]. Eur J Surg Oncol, 2004, 30(1): 85-87.
88. Esmer Sanchez D, Rangel D. Inflammatory pseudotumor of the retrope- ritioneum[J]. Rev Gastroenterol Mex, 2002, 67: 97-99.
89. Pascual-Ramos V, Duarte-Rojo A, Villa AR, et al. Systemic lupusery thematosus as a cause and prognostic factor of acute pancreatitis[J]. J Rheumatol, 2004, 31(4): 707-712.
90. Sanchez-Lozada RA, Costa-Rosero AV, Chapa-Azuela O, et al. Etiology on determining the severity of acute pancreatitis[J]. Gac Med Mex, 2003, 139 (1): 27-31.
91. Gullo L, Migliori M, Olah A, et al. Acute pancreatitis in five European countries∶etiology and mortality[J]. Pancreas, 2002, 24(3): 223-227.
92. 陈浩, 李非, 程韵枫, 等. 大鼠重症急性胰腺炎病情演变中中性白细胞的作用[J]. 世界华人消化杂志, 2001, 9(7): 776–779.
93. 谭至柔, 唐国都, 姜海行, 等. 抗氧化剂对急性胰腺炎大鼠核因子-KB和一氧化氮合酶的影响[J]. 世界华人消化杂志, 2004, 12(3): 711–713.
94. 张晓华, 李兆申, 屠振兴, 等. Caspase-1激活的细胞因子在实验性重症急性胰腺炎肺损伤中的作用[J]. 解放军医杂志, 2003, 28(12): 1074-1076.
95. 彭晓辉, 于剑波, 高宏凯, 等. 急性胰腺炎胰腺内源性RAS的活化与局部微循环P选择素表达变化规律的研究[J]. 华西医学, 2003, 18(4): 465-466.
96. Nagar AB, Go relick FS. A cute pancreatitis[J]. Curr Op in Gastroenterol, 2004, 20: 439-443.
97. Dominguez-Munoz JE, Effer B, Sauerbruch T, et al. Dynamics and factors related with the ERCP-induced elevation of serum pancreatic enzymes[J]. Digestion, 1995, 56: 290.
98. Jaffray C, Yang J, Carter G, et al. Pancreatic elastase activates pulmonary nuclear factor kappa B and inhibitory kappa B, mimicking pancreatitis-associated adult respiratory distress syndrome[J]. Surgery, 2000, 128(2): 225-231.
99. Werner J, Dragotakes SC, Fernandez-del Castillo C, et al. Technetium 299m- labeled white blood cells: a new method to define the local and systemic role of leukocytes in acute experimental pancre-atitis [J]. Ann Surg, 1998, 227(1): 86-94.
100.Bhatia M, Saluja AK, HofbauerB, et al. The effects of neutrophil depletion on a completely noninvasive model of acute pancreatitis-associated lung injury[J]. Int J Pancreatol, 1998, 24(2): 77-83.
101.Hartwig W, Werner J, Warshaw AL, et al. Membrane-bound ICAM-1 is up regulated by trypsin and contributes to leukocyte mi-gration in acute pancreatitis[J]. Am J Physiol Gastrointest Liver Physiol, 2004, 287(6): G11942-G1199.
102.Hartwig W, Carter EA, Jimenez RE, et al. Neutrophil metabolic activity but not neutrophil sequestration reflects the development of pancreatitis associated lung injury[J]. Crit CareMed, 2002, 30(9): 2075-2082.
103.Pereda J, Sabater L, Cassinello N, Gomez-Cambronero L, et al. Effect of imultaneous inhibition of TNF-alpha production and xan-thine oxidase in experimental acute pancreatitis: the role of mito-gen activated protein kinases[J]. Ann Surg, 2004, 240(1): 108-116.
104.Minter RM, Ferry MA, Murday ME, et al. Adenoviral delivery of human and viral IL-10 in murine sepsis[J]. J Immunol, 2001, 167(2): 1053-1059.
105.Osman MO, Kristensen JU, Jacobsen NO, et al. A monoclonal Anti- interleukin 8 antibody (WS24) inhibits cytokine response andacute lung injury in experimental severe acute necrotising pancreas-titis in rabbits [J]. Gut, 1998, 43(2): 232-239.
106.Maa J, Grady EF, Yoshimi SK, et al. Substance P is a determi-nant of lethality in diet-induced hemorrhagic pancreatitis in mice[J]. Surgery, 2000, 128(2): 232-239.
107.Shi X, Gao NR, Yin Y, et al. Role of neurokinin-1 receptor in lung injury in rats with acute necrotizing pancreatitis[J]. Zhong-guo Wei Zhong Bing Ji Jiu Yi Xue, 2003, 15(7): 422-425.
108.Lau HY, Wong FL, BhatiaM. A key role of neurokinin 1 receptors in acute pancreatitis and associated lung injury [J]. Biochem Biophys Res Commun, 2005, 327(2): 509-515.
109.Gray KD, Simovic MO, Chapman WC, et al. Systemic NF-kappa B activation in a transgenic mouse model of acute pancreatitis[J]. J Surg Res, 2003, 110(1): 310-314.
110.Ware LB, Matthay MA. The acute respiratory distress syndrome[J]. N Engl J Med, 2000, 342(18): 1334-1349.
111.BhatnagrA, Wig JD, Majumdar S. Expression of activation,adhesion molecules and intracellular cytokines in acute pancreatitis[J]. Immunol Lett, 2001, 77: 133-141.
112.Grewl HP,KotbM, Mohy EI Din A, et al. Induion of tumor necrosis Factor in severe acute pancreatitis and its subsequent re-dution after hepatic passage[J]. Surgery, 1994, 115: 213-221.
113.史君, 李春跃, 杨桂花. 白细胞介素-6与心血管疾病[J]. 内蒙古医学院学报, 2004, 26(1): 66-68.
114.Yoshimura T, Matsushima K, Oppenheim JJ, et al. Neutrophil chemotactic factor produced by lipopolysaccharide (LPS) stimulated human bloodmononuclear leukocytes: partial characterization and separation from interleukin 1(IL-1)[J]. J Immunol, 1987, 139: 788-793.
115.BaggioliniM. Chemokines in pathology and medicine [J]. J Intern Med, 2001, 250: 91-104.
116.Benveniste J , Henson PM, Cochrane CG, et al. Leukocyte dependent histamine release from rabbit p latelets. The role of IgE, basophils, and a platelet- activating factor[J]. J Exp Med, 1972, 136: 1356-1377.
117.Curley P, Nestor M, Collins K, et al. Decreased Interleukin-2 Production in Murine Acrte Pancreatitis: Potential for Immunomodulation [J]. Gastroenterology, 1996, 110(2): 583-588.
118.金忱, 倪泉兴, 张群华, 等. 急性胰腺炎大鼠TNF-α和IL-10 mRNA的表达及其意义[J]. 外科理论与实践, 2001, 6(6): 379-382.
119.王先坤, 詹乐恒, 王世文, 等. IL-10、IL-18 在重症急性胰腺炎肺损伤中的作用[J]. 中国普外基础与临床杂志, 2005, 12(5): 443-446.
120.邓群, 黎沾良, 姚咏明, 等. 急性坏死性胰腺炎早期血清细胞因子的变化及免疫干扰的影响[J]. 中国危重病急救医学, 1999, 11(6): 358-360.
121.尤家禄. 缺血-再灌注损伤[A]. 见: 王迪浔, 金惠铭, 主编. 病理生理学[M]. 北京:人民卫生出版社, 1995. 323-336.
122.魏捷, 秦兴雷, 鲁敏, 等. 重症急性胰腺炎微循环障碍的实验研究[J]. 实用诊断与治疗杂志, 2003, 17(3): 180-182.
123.金惠铭, 主编. 病理生理学[M]. 第5版. 北京: 人民卫生出版社, 2002. 153-156.
124.Chang CK, Albarillo MV, Schumer W. Therapeutic effect of dimethyl sulfoxide on ICAM-1 gene expression and activation of NF-kappB and AP-1 in septic rats[J]. J Surg Res, 2001, 95: 181-187.
125.郭莲怡,金旭鹏,李舒. 参附注射液对重症急性胰腺炎患者血浆内皮素、一氧化氮浓度的影响[J]. 中国中医急诊, 2007, 16(3): 298-299.
126.Schmidt H, Creutzfeldt W. The possible role of phospholipase A in the pathogenesis of acute pancreatitis[J]. Scand J Gastroenterol, 1969, 4(1): 39-48.
127.Kihara Y, Yoshikawa H, Honda H, et al. Natural disrup tion ofgroup 2 phospholipase A2 gene protects against choline-deficientethionine -supplemented diet-induced acute pancreatitis and lunginjury[J]. Pancreas, 2005, 31(1): 48-53.
128.Jaffray C, Yang J, Carter G, et al. Pancreatic elastase activates pulmonary nuclear factor kappa B and inhibitory kappa B, mimicking pancreatitis- associated adult respiratory distress syndrome[J].Surgery, 2000, 128(2): 225-231.
129.HartwigW, Carter EA, J imenez RE, et al. Neutrophil metabolic activity but not neutrophil sequestration reflects the development of pancreatitis -associated lung injury [J]. Crit CareMed, 2002, 30(9): 2075-2082.
130.张刚,张肇达, 等. 实验性急性胰腺炎大鼠肺内肿瘤坏死因子mRNA的表达及其意义[J]. 华西医科大学学报,1999, 30: 379-381.
131.Frossard JL, Saluja A, Bhagat L. The role of intercellular adhesion molecular 1 and neutrophils in acute pancreatits and pancreatits -associated lung injury[J]. Gastroenterology, 1999, 116: 694-701.
132.Tsukahara Y,Morisaki T,Horita Y.Role of nitric oxide derived from alveolar macrophages in the early phase of acute pancreatits[J]. J Surg Res, 1996, 66: 43-50.
133.Gray KD, Simovic MO, Chapman WC, et al. Systemic NF-kappaB activation in a transgenic mouse model of acute pancreatitis[J]. J Surg Res, 2003, 110(1): 310-314.
134.Ethridge RT, Hashimoto K, ChungDH, et al. Selective inhibition of NF- kappaB attenuates the severity of cerulean-induced acute pancreatitis [J]. J Am Coll Surg, 2002, 195(4): 497-505.
135.Frossard JL, Kwak B, Chanson M, et al. Cd40 ligand-deficient mice are protected against cerulean-induced acute ancreatitis and pancreatitis -associated lung injury[J]. Gastroenterology, 2001, 121(1): 184-194.
136.Ware LB, Matthay MA. The acute respiratory distress syndrome [J]. N Engl J Med, 2000, 342(18): 1334-1349.
137.Reid PT, Marsden ME, Cunninghain GA, et al. Human neutrophil elastase regulates t he expression and secretion of Elafin in type Ⅱ alveolar epit helial cells[J]. Federa Eur Biochem Soc, 1999, 457(1): 33-37.
138.Anne EK, Kevin M , Sallenare JM,et al. Differential regulation of secretory leukocyte protease inhibitor and elafin by progesterone[J]. Biochem Biophys Res Communi, 2003, 310(2): 594-599.
139.Yoshihiko S, Nobutaka L, Hiroshi A, et al. Expression of tissue trans glutaminase and elafin in human coronary: implication for plaque instability[J]. At herosclerosis, 2002, 160(1): 31-39.
140.Naoya Y, Hiroshi E , Hidenobu K, et al . Immunohistochemical expression of SKALP/ elafin in squamous cell carcinoma of human lung and esophagus. Int Congress Series ,2003 ,1255 (5) :299-303.