李春生 1 , 蔡雷 1 , 王銀平 1 , 楊榮 2 , 張煦 3
  • 1.上海復(fù)旦大學(xué)醫(yī)學(xué)院附屬華山醫(yī)院南匯分院、南匯中心醫(yī)院普外科一病區(qū)(上海 201300);;
  • 2.甘肅省腫瘤醫(yī)院病理科(蘭州 730050);;
  • 3.蘭州大學(xué)醫(yī)學(xué)院病理教研室(蘭州 730000);

目的　 研究環(huán)氧合酶-2(COX-2)在重癥急性胰腺炎(SAP)大鼠肝組織中的表達(dá),探討COX-2在SAP肝臟損傷中的作用。
方法 　以3.5%?；悄懰徕c胰膽管逆行注射誘導(dǎo)大鼠SAP模型。隨機分為對照組和SAP組，術(shù)后4、8、16及24 h測定血清淀粉酶(AMY)、丙氨酸氨基轉(zhuǎn)移酶(ALT)、天冬氨酸氨基轉(zhuǎn)移酶(AST)、腫瘤壞死因子(TNF)-α水平和腹水AMY; 光鏡下觀察胰腺和肝組織損傷情況; 免疫組化方法檢測COX-2在肝組織中的表達(dá)。
結(jié)果 　SAP組各時間點血清AMY、ALT、AST、TNF-α及腹水AMY水平均較對照組明顯升高,差異均有統(tǒng)計學(xué)意義(P lt;0.05),與胰腺和肝臟組織的病理學(xué)改變相一致。術(shù)后不同時相COX-2在肝組織中的表達(dá)陽性率明顯高于對照組,差異均有統(tǒng)計學(xué)意義(P lt;0.05),COX-2表達(dá)與ALT(rs=0.949,P=0.039)、AST(rs=0.972,P=0.016)及血清AMY(rs=0.944,P=0.041)呈正相關(guān)。
結(jié)論 　SAP時COX-2表達(dá)上調(diào)可能在SAP合并肝臟損傷中發(fā)揮重要作用。

引用本文： 李春生,蔡雷,王銀平,楊榮,張煦. COX-2在重癥急性胰腺炎所致肝臟損傷中的作用. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(4): 343-347. doi: 復(fù)制

1. Aoki H, Ohnishi H, Hama K, et al. Cyclooxygenase-2 is required for activated pancreatic stellate cells to respond to proinflammatory cytokines [J]. Am J Physiol Cell Physiol, 2007 ; 292(1): C259-C268.
2. 　O’Brien G, Shields CJ, Winter DC, et al. Cyclooxygenase-2 plays a central role in the genesis of pancreatitis and associated lung injury [J]. Hepatobiliary Pancreat Dis Int, 2005; 4(1): 126-129.
3. 　Ethridge RT, Chung DH, Slogoff M, et al. Cyclooxygenase-2 gene disruption attenuates the severity of acute pancreatitis and pancreatitis-associated lung injury [J]. Gastroenterology, 2002; 123(4): 1311-1322.
4. 　Aho HJ, Koskensalo SM, Nevalainen TJ. Experimental pancreatitis in the rat. Sodium taurocholate-induced acute haemorrhagic pancreatitis [J]. Scand J Gastroenterol, 1980; 15(4): 411-416.
5. 　Andrzejewska A, Dugosz J, Kurasz S, et al. Ultrastructure of liver in acute experimental pancreatitis in dogs treated with prostacyclin [J]. Exp Pathol, 1987; 31(1): 25-31.
6. 　Isogai M, Yamaguchi A, Hori A, et al. Hepatic histopathological changes in biliary pancreatitis [J]. Am J Gastroenterol, 1995; 90(3): 449-454.
7. 　Norman J. The role of cytokines in the pathogenesis of acute pancreatitis [J]. Am J Surg, 1998; 175(1): 76-83.
8. 　Bhanot UK, Mller P. Mechanisms of parenchymal injury and signaling pathways in ectatic ducts of chronic pancreatitis: implications for pancreatic carcinogenesis [J]. Lab Invest, 2009; 89(5): 489-497.
9. 　Toomey DP, Murphy JF, Conlon KC. COX-2, VEGF and tumour angiogenesis [J]. Surgeon, 2009; 7(3): 174-180.
10. 　Chien MH, Ku CC, Johansson G, et al. Vascular endothelial growth factor-C (VEGF-C) promotes angiogenesis by induction of COX-2 in leukemic cells via the VEGF-R3/JNK/AP-1 pathway [J]. Carcinogenesis, 2009 Oct 13 [Epub ahead of print].
11. 　Bastos-Pereira AL, Lugarini D, de Oliveira-Christoff A, et al. Celecoxib prevents tumor growth in an animal model by a COX-2 independent mechanism [J]. Cancer Chemother Pharmacol, 2010; 65(2): 267-276.
12. 　Chen B, Su B, Chen S. A COX-2 inhibitor nimesulide analog selectively induces apoptosis in Her2 overexpressing breast cancer cells via cytochrome c dependent mechanisms [J]. Biochem Pharmacol, 2009; 77(12): 1787-1794.
13. 　Menczer J, Schreiber L, Kravtsov V, et al. Cox-2 immunohistochemical expression in epithelial ovarian carcinoma and platin sensitivity [J]. Eur J Gynaecol Oncol, 2009; 30(5): 531-535.
14. 　李斌, 李玉民, 李汛, 等. 環(huán)氧合酶-2 對膿毒癥大鼠肝損傷的影響 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008; 15(4): 266-270.
15. 　張寧, 陶凱雄, 王國斌, 等. 環(huán)氧合酶-2及血管生成素-2在大腸癌中的表達(dá)及臨床意義 [J]. 中國普外基礎(chǔ)與臨床雜志, 2006; 13(5): 564-567.
  1. 1. Aoki H, Ohnishi H, Hama K, et al. Cyclooxygenase-2 is required for activated pancreatic stellate cells to respond to proinflammatory cytokines [J]. Am J Physiol Cell Physiol, 2007 ; 292(1): C259-C268.
  2. 2. 　O’Brien G, Shields CJ, Winter DC, et al. Cyclooxygenase-2 plays a central role in the genesis of pancreatitis and associated lung injury [J]. Hepatobiliary Pancreat Dis Int, 2005; 4(1): 126-129.
  3. 3. 　Ethridge RT, Chung DH, Slogoff M, et al. Cyclooxygenase-2 gene disruption attenuates the severity of acute pancreatitis and pancreatitis-associated lung injury [J]. Gastroenterology, 2002; 123(4): 1311-1322.
  4. 4. 　Aho HJ, Koskensalo SM, Nevalainen TJ. Experimental pancreatitis in the rat. Sodium taurocholate-induced acute haemorrhagic pancreatitis [J]. Scand J Gastroenterol, 1980; 15(4): 411-416.
  5. 5. 　Andrzejewska A, Dugosz J, Kurasz S, et al. Ultrastructure of liver in acute experimental pancreatitis in dogs treated with prostacyclin [J]. Exp Pathol, 1987; 31(1): 25-31.
  6. 6. 　Isogai M, Yamaguchi A, Hori A, et al. Hepatic histopathological changes in biliary pancreatitis [J]. Am J Gastroenterol, 1995; 90(3): 449-454.
  7. 7. 　Norman J. The role of cytokines in the pathogenesis of acute pancreatitis [J]. Am J Surg, 1998; 175(1): 76-83.
  8. 8. 　Bhanot UK, Mller P. Mechanisms of parenchymal injury and signaling pathways in ectatic ducts of chronic pancreatitis: implications for pancreatic carcinogenesis [J]. Lab Invest, 2009; 89(5): 489-497.
  9. 9. 　Toomey DP, Murphy JF, Conlon KC. COX-2, VEGF and tumour angiogenesis [J]. Surgeon, 2009; 7(3): 174-180.
  10. 10. 　Chien MH, Ku CC, Johansson G, et al. Vascular endothelial growth factor-C (VEGF-C) promotes angiogenesis by induction of COX-2 in leukemic cells via the VEGF-R3/JNK/AP-1 pathway [J]. Carcinogenesis, 2009 Oct 13 [Epub ahead of print].
  11. 11. 　Bastos-Pereira AL, Lugarini D, de Oliveira-Christoff A, et al. Celecoxib prevents tumor growth in an animal model by a COX-2 independent mechanism [J]. Cancer Chemother Pharmacol, 2010; 65(2): 267-276.
  12. 12. 　Chen B, Su B, Chen S. A COX-2 inhibitor nimesulide analog selectively induces apoptosis in Her2 overexpressing breast cancer cells via cytochrome c dependent mechanisms [J]. Biochem Pharmacol, 2009; 77(12): 1787-1794.
  13. 13. 　Menczer J, Schreiber L, Kravtsov V, et al. Cox-2 immunohistochemical expression in epithelial ovarian carcinoma and platin sensitivity [J]. Eur J Gynaecol Oncol, 2009; 30(5): 531-535.
  14. 14. 　李斌, 李玉民, 李汛, 等. 環(huán)氧合酶-2 對膿毒癥大鼠肝損傷的影響 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008; 15(4): 266-270.
  15. 15. 　張寧, 陶凱雄, 王國斌, 等. 環(huán)氧合酶-2及血管生成素-2在大腸癌中的表達(dá)及臨床意義 [J]. 中國普外基礎(chǔ)與臨床雜志, 2006; 13(5): 564-567.