• 1.四川省德陽市人民醫(yī)院普外科（德陽 618000）;;
  • 2.昆明醫(yī)學(xué)院第一附屬醫(yī)院普外科（昆明 650032）;

目的  探討急性化膿性腹膜炎相關(guān)性腹水（ASPAAF）誘導(dǎo)大鼠肝臟損傷的作用及其機(jī)理。
方法  將32只SD大鼠（雌雄不拘）隨機(jī)分為2組： ASPAAF組（n=16）和對照組（n=16），分別向腹腔內(nèi)注射ASPAAF 和生理鹽水，每只8 ml。于腹腔注射后6 h 和12 h分批處死大鼠，每時(shí)間點(diǎn)8只。檢測血清內(nèi)毒素及TNF-α水平和肝功能（AST、ALT和STB）； 檢測肝臟組織TNF-α水平； 光鏡下觀察肝臟組織損傷情況。
結(jié)果  于腹腔注射后6 h 和12 h，ASPAAF組血清內(nèi)毒素、TNF-α、AST、ALT和STB水平以及肝臟組織TNF-α水平均較對照組高 (P＜0.05)； 以上指標(biāo)在ASPAAF組組內(nèi)隨時(shí)間的增加而顯著增高(P＜0.05)； ASPAAF組肝臟組織細(xì)胞出現(xiàn)水腫，甚至點(diǎn)狀壞死，6 h 和12 h間無明顯差別，對照組肝臟組織細(xì)胞正常。
結(jié)論  ASPAAF能引起大鼠肝臟損傷，內(nèi)毒素和TNF-α在這一損傷過程中發(fā)揮了重要作用。

引用本文： 方向,陳玉祥,劉震,程若川,張躍天,李俊. 急性化膿性腹膜炎相關(guān)性腹水對大鼠肝臟的損傷作用研究. 中國普外基礎(chǔ)與臨床雜志, 2009, 16(7): 555-559. doi: 復(fù)制

1. 姚詠明， 盛志勇． 我國創(chuàng)傷膿毒癥基礎(chǔ)研究新進(jìn)展 [Ｊ]. 中華創(chuàng)傷雜志， 2003； 19(1): 912.
2. Yang S, Koo DJ, Chaudry IH, et al. Glycine attenuates hepatocellular depression during early sepsis and reduces sepsisinduced mortality [Ｊ]. Crit Care Med, 2001; 29(6): 1201 1206.
3. Erwin PJ, Lewis H, Dolan S, et al. Lipopolysaccharide binding protein in acute pancreatitis [Ｊ]. Crit Care Med, 2000; 28(1): 104109.
4. Makhija R, Kingsnorth AN. Cytokine storm in acute pancreatitis [Ｊ]. J Hepatobiliary Pancreat Surg, 2002; 9(4): 401410.
5. Davies MG, Hagen PO. Systemic inflammatory response syndrome [Ｊ]. Br J Surg, 1997; 84 (7): 920935.
6. Liu D, Li C, Chen Y, et al. Nuclear import of proinflammatory transcription factors is required for massive liver apoptosis induced by bacterial lipopolysaccharide [Ｊ]. J Biol Chem, 2004; 279(46): 4843448442.
7. Sass G, Heinlein S, Agli A, et al. Cytokine expression in three mouse models of experimental hepatitis [Ｊ]. Cytokine, 2002; 19(3): 115120.
8. 蔣力生， 陳鵬. 膿毒癥與內(nèi)毒素血癥的治療現(xiàn)狀與展望 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志， 2004； 11(6): 551553.
9. 宋文哲， 宋燕， 譚巖， 等. 氨基胍對內(nèi)毒素休克大鼠肝損傷的保護(hù)作用研究 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志， 2003； 10(4): 347350.
10. Thirunavukkarasu C, Uemura T, Wang LF, et al. Normal rat hepatic stellate cells respond to endotoxin in LBPindependent manner to produce inhibitor(s) of DNA synthesis in hepatocytes [Ｊ]. J Cell Physiol, 2005; 204(4): 654665.[11]Schwabe RF, Brenner DA. Mechanisms of liver injury. I. TNF induced liver injury: role of IKK, JNK, and ROS pathways [Ｊ]. Am J Physiol Gastrointest Liver Physiol, 2006; 290(4): G583G589.
11. Skinner NA, MacIsaac CM, Hamilton JA, et al. Regulation of Tolllike receptor (TLR) 2 and TLR4 on CD14dimCD16+ monocytes in response to sepsisrelated antigens [Ｊ]. Clin Exp Immunol, 2005; 141(2): 270278.
12. Kobayashi Y, Mori M, Naruto T, et al. Dynamic movement of cytochrome c from mitochondria into cytosol and peripheral circulation in massive hepatic cell injury [Ｊ]. Pediatr Int 2004; 46(6): 685692.
13. 石力， 田伏洲， 李旭， 等. 急性胰腺炎大鼠肝臟NFκB對TNFα表達(dá)的調(diào)控及其在肝損傷中的作用 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志， 2004； 11(3): 228230.
14. GómezCambronero LG, Sabater L, Pereda J, et al. Role of cytokines and oxidative stress in the pathophysiology of acute pancreatitis: therapeutical implications [Ｊ]. Curr Drug Targets Inflamm Allergy, 2002; 1(4): 393403.
15. Pastor CM, Frossard JL. Are genetically modified mice useful for the understanding of acute pancreatitis? [Ｊ]. FASEB J, 2001; 15(6): 893897.
16. Leindler L, Morschl E, László F, et al. Importance of cytokines, nitric oxide, and apoptosis in the pathological process of necrotizing pancreatitis in rats [Ｊ]. Pancreas, 2004; 29(2): 157161.
17. Vliagoftis H, Befus AD, Hollenberg MD, et al. Airway epithelial cells release eosinophil survivalpromoting factors (GMCSF) after stimulation of proteinaseactivated receptor 2 [Ｊ]. J Allergy Clin Immunol, 2001； 107(4): 679685.
18. Van Pelt LJ, Huisman MV, Weening RS, et al. A single dose of granulocytemacrophage colony stimulating factor induces systemic interleukin8 release and neutrophil activation in healthy volunteers [Ｊ]. Blood, 1996; 87(12): 53055313.
19. Jean LF, Ashok KS, Nicolas M, et al. In vivo evidence for the role of GMCSF as a mediator in acute pancreatitisassociated lung injury [Ｊ]. Am J Physiol Lung Cell Mol Physiol, 2002; 283(3): 541548.
20. O’Neill S, O’Neill AJ, Conroy E, et al. Altered caspase expression results in delayed neutrophil apoptosis in acute pancreatitis [Ｊ]. J Leukoc Biol, 2000; 68(1): 1520.
21. Botha AJ, Moore FA, Moore EE, et al. Early neutrophil sequestration after injury: a pathogenic mechanism for multiple organ failure [Ｊ]. J Trauma, 1995; 39(3): 411417.
22. 劉震， 程若川， 方向， 等. PAAF與ASPAAF誘導(dǎo)的腸損傷比較的實(shí)驗(yàn)研究 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志， 2008； 15(8): 555559.
23. 陳哲宇， 齊清會(huì)， 嚴(yán)律南. 細(xì)菌性腹膜炎誘導(dǎo)大鼠多器官功能不全綜合征后結(jié)腸運(yùn)動(dòng)的變化 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志， 2006； 13(3): 287290.
24. 肖菲， 康焰. 腸道細(xì)菌移位的研究現(xiàn)狀 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志， 2006； 13(2): 240243.
  1. 1. 姚詠明， 盛志勇． 我國創(chuàng)傷膿毒癥基礎(chǔ)研究新進(jìn)展 [Ｊ]. 中華創(chuàng)傷雜志， 2003； 19(1): 912.
  2. 2. Yang S, Koo DJ, Chaudry IH, et al. Glycine attenuates hepatocellular depression during early sepsis and reduces sepsisinduced mortality [Ｊ]. Crit Care Med, 2001; 29(6): 1201 1206.
  3. 3. Erwin PJ, Lewis H, Dolan S, et al. Lipopolysaccharide binding protein in acute pancreatitis [Ｊ]. Crit Care Med, 2000; 28(1): 104109.
  4. 4. Makhija R, Kingsnorth AN. Cytokine storm in acute pancreatitis [Ｊ]. J Hepatobiliary Pancreat Surg, 2002; 9(4): 401410.
  5. 5. Davies MG, Hagen PO. Systemic inflammatory response syndrome [Ｊ]. Br J Surg, 1997; 84 (7): 920935.
  6. 6. Liu D, Li C, Chen Y, et al. Nuclear import of proinflammatory transcription factors is required for massive liver apoptosis induced by bacterial lipopolysaccharide [Ｊ]. J Biol Chem, 2004; 279(46): 4843448442.
  7. 7. Sass G, Heinlein S, Agli A, et al. Cytokine expression in three mouse models of experimental hepatitis [Ｊ]. Cytokine, 2002; 19(3): 115120.
  8. 8. 蔣力生， 陳鵬. 膿毒癥與內(nèi)毒素血癥的治療現(xiàn)狀與展望 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志， 2004； 11(6): 551553.
  9. 9. 宋文哲， 宋燕， 譚巖， 等. 氨基胍對內(nèi)毒素休克大鼠肝損傷的保護(hù)作用研究 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志， 2003； 10(4): 347350.
  10. 10. Thirunavukkarasu C, Uemura T, Wang LF, et al. Normal rat hepatic stellate cells respond to endotoxin in LBPindependent manner to produce inhibitor(s) of DNA synthesis in hepatocytes [Ｊ]. J Cell Physiol, 2005; 204(4): 654665.[11]Schwabe RF, Brenner DA. Mechanisms of liver injury. I. TNF induced liver injury: role of IKK, JNK, and ROS pathways [Ｊ]. Am J Physiol Gastrointest Liver Physiol, 2006; 290(4): G583G589.
  11. 11. Skinner NA, MacIsaac CM, Hamilton JA, et al. Regulation of Tolllike receptor (TLR) 2 and TLR4 on CD14dimCD16+ monocytes in response to sepsisrelated antigens [Ｊ]. Clin Exp Immunol, 2005; 141(2): 270278.
  12. 12. Kobayashi Y, Mori M, Naruto T, et al. Dynamic movement of cytochrome c from mitochondria into cytosol and peripheral circulation in massive hepatic cell injury [Ｊ]. Pediatr Int 2004; 46(6): 685692.
  13. 13. 石力， 田伏洲， 李旭， 等. 急性胰腺炎大鼠肝臟NFκB對TNFα表達(dá)的調(diào)控及其在肝損傷中的作用 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志， 2004； 11(3): 228230.
  14. 14. GómezCambronero LG, Sabater L, Pereda J, et al. Role of cytokines and oxidative stress in the pathophysiology of acute pancreatitis: therapeutical implications [Ｊ]. Curr Drug Targets Inflamm Allergy, 2002; 1(4): 393403.
  15. 15. Pastor CM, Frossard JL. Are genetically modified mice useful for the understanding of acute pancreatitis? [Ｊ]. FASEB J, 2001; 15(6): 893897.
  16. 16. Leindler L, Morschl E, László F, et al. Importance of cytokines, nitric oxide, and apoptosis in the pathological process of necrotizing pancreatitis in rats [Ｊ]. Pancreas, 2004; 29(2): 157161.
  17. 17. Vliagoftis H, Befus AD, Hollenberg MD, et al. Airway epithelial cells release eosinophil survivalpromoting factors (GMCSF) after stimulation of proteinaseactivated receptor 2 [Ｊ]. J Allergy Clin Immunol, 2001； 107(4): 679685.
  18. 18. Van Pelt LJ, Huisman MV, Weening RS, et al. A single dose of granulocytemacrophage colony stimulating factor induces systemic interleukin8 release and neutrophil activation in healthy volunteers [Ｊ]. Blood, 1996; 87(12): 53055313.
  19. 19. Jean LF, Ashok KS, Nicolas M, et al. In vivo evidence for the role of GMCSF as a mediator in acute pancreatitisassociated lung injury [Ｊ]. Am J Physiol Lung Cell Mol Physiol, 2002; 283(3): 541548.
  20. 20. O’Neill S, O’Neill AJ, Conroy E, et al. Altered caspase expression results in delayed neutrophil apoptosis in acute pancreatitis [Ｊ]. J Leukoc Biol, 2000; 68(1): 1520.
  21. 21. Botha AJ, Moore FA, Moore EE, et al. Early neutrophil sequestration after injury: a pathogenic mechanism for multiple organ failure [Ｊ]. J Trauma, 1995; 39(3): 411417.
  22. 22. 劉震， 程若川， 方向， 等. PAAF與ASPAAF誘導(dǎo)的腸損傷比較的實(shí)驗(yàn)研究 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志， 2008； 15(8): 555559.
  23. 23. 陳哲宇， 齊清會(huì)， 嚴(yán)律南. 細(xì)菌性腹膜炎誘導(dǎo)大鼠多器官功能不全綜合征后結(jié)腸運(yùn)動(dòng)的變化 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志， 2006； 13(3): 287290.
  24. 24. 肖菲， 康焰. 腸道細(xì)菌移位的研究現(xiàn)狀 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志， 2006； 13(2): 240243.