• 1.中國醫(yī)科大學附屬第一醫(yī)院重癥醫(yī)學科(遼寧沈陽 110001);;
  • 2.中國醫(yī)科大學附屬第一醫(yī)院普通外科(遼寧沈陽 110001);

目的  研究高遷移率族蛋白B1 (high mobility group box-1 protein,HMGB1) mRNA表達對急性壞死性胰腺炎(acute necrotizing pancreatitis,ANP)大鼠腸黏膜緊密連接蛋白-1 (zonula occludens protein-1,ZO-1)表達的影響,初步探討ANP時腸黏膜屏障損傷的可能機理。
方法  將96只Wistar大鼠隨機(隨機數字表法)均分為ANP組、丙酮酸乙酯(EP)組及假手術組,3組均分別于術后6、12、24及48h時各抽取8只大鼠,取腹主動脈血和回腸組織。采用全自動生化分析儀檢測血淀粉酶(AMY)水平,采用改良酶學分光光度法檢測血漿D-乳酸水平,采用硫代巴比妥酸(TAB)比色法檢測回腸組織丙二醛(MDA)含量,采用HE染色法觀察大鼠回腸組織的病理學改變,采用免疫組織化學法(SP法)觀察回腸組織ZO-1蛋白的表達,采用逆轉錄聚合酶鏈反應(RT-PCR)法檢測回腸組織HMGB1和ZO-1mRNA的表達。
結果  各時相EP組大鼠的血AMY、D-乳酸和回腸組織MDA含量均低于ANP組(P<0.05)。6h時,ANP組大鼠回腸組織HMGB1mRNA的表達即上調,但ZO-1mRNA的表達下調;各時相EP組大鼠回腸組織HMGB1mRNA的表達水平均低于ANP組,但ZO-1mRNA的表達水平均高于ANP組(P<0.05)。各時相EP組大鼠回腸組織的病理學損傷均較ANP組明顯減輕。
結論  ANP大鼠回腸黏膜組織中ZO-1表達下調是ANP大鼠腸黏膜屏障損傷的重要原因之一,可能與炎癥介質HMGB1的過度表達有關。

引用本文: 欒正剛,郭仁宣. HMGB1 mRNA表達對急性壞死性胰腺炎大鼠腸黏膜ZO-1 mRNA及其蛋白表達的影響△. 中國普外基礎與臨床雜志, 2013, 20(3): 265-270. doi: 復制

1. Pitchumoni CS, Patel NM, Shah P. Factors influencing mortality in acute pancreatitis:can we alter them?[J]. J Clin Gastroenterol, 2005, 39(9):798-814.
2. Bank S, Singh P, Pooran N, et al. Evaluation of factors that have reduced mortality from acute pancreatitis over the past 20 years[J]. J Clin Gastroenterol, 2002, 35(1):50-60.
3. Jamdar S, Siriwardena AK. Contemporary management ofinfected necrosis complicating severe acute pancreatitis[J]. Crit Care, 2006, 10(1):101.
4. 刁永鵬, 陳宏, 李非. 重癥急性胰腺炎腸屏障功能障礙的研究進展[J]. 中國普外基礎與臨床雜志, 2009, 16(7):588-592.
5. 王琛, 樊勇. 急性胰腺炎常見并發(fā)癥及防治[J]. 中國普外基礎與臨床雜志, 2010, 17(10):1107-1108.
6. Blikslager AT, Moeser AJ, Gookin JL, et al. Restoration of barrier function in injured intestinal mucosa[J]. Physiol Rev, 2007, 87(2):545-564.
7. Li Q, Zhang Q, Wang M, et al. Interferon-gamma and tumor necrosis factor-alpha disrupt epithelial barrier function by alteringlipid composition in membrane microdomains of tight junction[J]. Clin Immunol, 2008, 126(1):67-80.
8. 曹洪慶, 黃鶴光, 陳燕昌, 等. 重癥急性胰腺炎大鼠緊密連接蛋白-1的表達與腸黏膜屏障損傷[J]. 中國普外基礎與臨床雜志, 2011, 18(3):240-244.
9. 高志光, 秦環(huán)龍. 腸上皮細胞緊密連接的生物學功能及在腸屏障中的作用[J]. 腸外與腸內營養(yǎng), 2005, 12(5):299-302.
10. Wang H, Yang H, Tracey KJ. Extracellular role of HMGB1 in infla-mmation and sepsis[J]. J Intern Med, 2004, 255(3):320-331.
11. Luan ZG, Zhang H, Ma XC, et al. Role of high-mobility group box 1 protein in the pathogenesis of intestinal barrier injury in rats with severe acute pancreatitis[J]. Pancreas, 2010, 39(2):216-223.
12. Aho HJ, Koskensalo SM, Nevalainen TJ. Experimental pancreatitisin the rat. Sodium taurocholate-induced acute haemorrhagic pancreatitis[J]. Scand J Gastroenterol, 1980, 15(4):411-416.
13. Gerlach H. Risk management in patients with severe acute pancreatitis[J]. Crit Care, 2004, 8(6):430-432.
14. Heinrich S, Schäfer M, Rousson V, et al. Evidence-based treatment of acute pancreatitis:a look at established paradigms[J]. Ann Surg, 2006, 243(2):154-168.
15. Ammori BJ. Role of the gut in the course of severe acute pancreatitis[J]. Pancreas, 2003, 26(2):122-129.
16. Dervenis C, Smailis D, Hatzitheoklitos E. Bacterial translocation and its prevention in acute pancreatitis[J]. J Hepatobiliary Pancreat Surg, 2003, 10(6):415-418.
17. Furuya T, Soeno T, Komatsu M. Strategy for bacterial translocation in acute pancreatitis[J]. Nippon Shokakibyo Gakkai Zasshi, 2004, 101(5):502-509.
18. Chen X, Zhao HX, Fu XS, et al. Glucagonlike peptide 2 protectsintestinal barrier in severe acute pancreatitis through regulating intestinal epithelial cell proliferation and apoptosis[J]. Pancreas,.
19. Wang X, Wang B, Wu J, et al. Beneficial effects of growth hormone on bacterial translocation during the course of acute necroti-zing pancreatitis in rats[J]. Pancreas, 2001, 23(2):148-156.
20. Nusrat A, Turner JR, Madara JL. Molecular physiology and pathophysiology of tight junctions.Ⅳ. Regulation of tight junctions by extracellular stimuli:nutrients, cytokines, and immune cells[J]. Am J Physiol Gastrointest Liver Physiol, 2000, 279(5):G851-G857.
21. 秦勇, 黨曉燕. 白藜蘆醇對重癥急性胰腺炎大鼠腸黏膜缺血-再灌注損傷的保護作用[J]. 中國普外基礎與臨床雜志, 2009, 16(10):819-823.
22. Mazzon E, Sturniolo GC, Puzzolo D, et al. Effect of stress on the paracellular barrier in the rat ileum[J]. Gut, 2002, 51(4):507-513.
23. Stevenson BR, Siliciano JD, Mooseker MS, et al. Identification of ZO-1:a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia[J]. J Cell Biol, 1986, 103(3):755-766.
24. Fink MP. Ethyl pyruvate:a novel anti-inflammatory agent[J]. J Intern Med, 2007, 261(4):349-362.
25. Yang R, Uchiyama T, Alber SM, et al. Ethyl pyruvate ameliorates distant organ injury in a murine model of acute necrotizing pancreatitis[J]. Crit Care Med, 2004, 32(7):1453-1459.
26. Ulloa L, Ochani M, Yang H, et al. Ethyl pyruvate prevents lethalityin mice with established lethal sepsis and systemic inflammation[J]. Proc Natl Acad Sci U S A, 2002, 99(19):12351-12356.
27. , 41(7):1080-1085.
  1. 1. Pitchumoni CS, Patel NM, Shah P. Factors influencing mortality in acute pancreatitis:can we alter them?[J]. J Clin Gastroenterol, 2005, 39(9):798-814.
  2. 2. Bank S, Singh P, Pooran N, et al. Evaluation of factors that have reduced mortality from acute pancreatitis over the past 20 years[J]. J Clin Gastroenterol, 2002, 35(1):50-60.
  3. 3. Jamdar S, Siriwardena AK. Contemporary management ofinfected necrosis complicating severe acute pancreatitis[J]. Crit Care, 2006, 10(1):101.
  4. 4. 刁永鵬, 陳宏, 李非. 重癥急性胰腺炎腸屏障功能障礙的研究進展[J]. 中國普外基礎與臨床雜志, 2009, 16(7):588-592.
  5. 5. 王琛, 樊勇. 急性胰腺炎常見并發(fā)癥及防治[J]. 中國普外基礎與臨床雜志, 2010, 17(10):1107-1108.
  6. 6. Blikslager AT, Moeser AJ, Gookin JL, et al. Restoration of barrier function in injured intestinal mucosa[J]. Physiol Rev, 2007, 87(2):545-564.
  7. 7. Li Q, Zhang Q, Wang M, et al. Interferon-gamma and tumor necrosis factor-alpha disrupt epithelial barrier function by alteringlipid composition in membrane microdomains of tight junction[J]. Clin Immunol, 2008, 126(1):67-80.
  8. 8. 曹洪慶, 黃鶴光, 陳燕昌, 等. 重癥急性胰腺炎大鼠緊密連接蛋白-1的表達與腸黏膜屏障損傷[J]. 中國普外基礎與臨床雜志, 2011, 18(3):240-244.
  9. 9. 高志光, 秦環(huán)龍. 腸上皮細胞緊密連接的生物學功能及在腸屏障中的作用[J]. 腸外與腸內營養(yǎng), 2005, 12(5):299-302.
  10. 10. Wang H, Yang H, Tracey KJ. Extracellular role of HMGB1 in infla-mmation and sepsis[J]. J Intern Med, 2004, 255(3):320-331.
  11. 11. Luan ZG, Zhang H, Ma XC, et al. Role of high-mobility group box 1 protein in the pathogenesis of intestinal barrier injury in rats with severe acute pancreatitis[J]. Pancreas, 2010, 39(2):216-223.
  12. 12. Aho HJ, Koskensalo SM, Nevalainen TJ. Experimental pancreatitisin the rat. Sodium taurocholate-induced acute haemorrhagic pancreatitis[J]. Scand J Gastroenterol, 1980, 15(4):411-416.
  13. 13. Gerlach H. Risk management in patients with severe acute pancreatitis[J]. Crit Care, 2004, 8(6):430-432.
  14. 14. Heinrich S, Schäfer M, Rousson V, et al. Evidence-based treatment of acute pancreatitis:a look at established paradigms[J]. Ann Surg, 2006, 243(2):154-168.
  15. 15. Ammori BJ. Role of the gut in the course of severe acute pancreatitis[J]. Pancreas, 2003, 26(2):122-129.
  16. 16. Dervenis C, Smailis D, Hatzitheoklitos E. Bacterial translocation and its prevention in acute pancreatitis[J]. J Hepatobiliary Pancreat Surg, 2003, 10(6):415-418.
  17. 17. Furuya T, Soeno T, Komatsu M. Strategy for bacterial translocation in acute pancreatitis[J]. Nippon Shokakibyo Gakkai Zasshi, 2004, 101(5):502-509.
  18. 18. Chen X, Zhao HX, Fu XS, et al. Glucagonlike peptide 2 protectsintestinal barrier in severe acute pancreatitis through regulating intestinal epithelial cell proliferation and apoptosis[J]. Pancreas,.
  19. 19. Wang X, Wang B, Wu J, et al. Beneficial effects of growth hormone on bacterial translocation during the course of acute necroti-zing pancreatitis in rats[J]. Pancreas, 2001, 23(2):148-156.
  20. 20. Nusrat A, Turner JR, Madara JL. Molecular physiology and pathophysiology of tight junctions.Ⅳ. Regulation of tight junctions by extracellular stimuli:nutrients, cytokines, and immune cells[J]. Am J Physiol Gastrointest Liver Physiol, 2000, 279(5):G851-G857.
  21. 21. 秦勇, 黨曉燕. 白藜蘆醇對重癥急性胰腺炎大鼠腸黏膜缺血-再灌注損傷的保護作用[J]. 中國普外基礎與臨床雜志, 2009, 16(10):819-823.
  22. 22. Mazzon E, Sturniolo GC, Puzzolo D, et al. Effect of stress on the paracellular barrier in the rat ileum[J]. Gut, 2002, 51(4):507-513.
  23. 23. Stevenson BR, Siliciano JD, Mooseker MS, et al. Identification of ZO-1:a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia[J]. J Cell Biol, 1986, 103(3):755-766.
  24. 24. Fink MP. Ethyl pyruvate:a novel anti-inflammatory agent[J]. J Intern Med, 2007, 261(4):349-362.
  25. 25. Yang R, Uchiyama T, Alber SM, et al. Ethyl pyruvate ameliorates distant organ injury in a murine model of acute necrotizing pancreatitis[J]. Crit Care Med, 2004, 32(7):1453-1459.
  26. 26. Ulloa L, Ochani M, Yang H, et al. Ethyl pyruvate prevents lethalityin mice with established lethal sepsis and systemic inflammation[J]. Proc Natl Acad Sci U S A, 2002, 99(19):12351-12356.
  27. 27. , 41(7):1080-1085.
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