• 1.蘭州大學(xué)第二醫(yī)院普通外科 (甘肅蘭州 730030);;
  • 2.甘肅省緊急醫(yī)療救援中心 (甘肅蘭州 730030);;
  • 3.甘肅省第二人民醫(yī)院普外科 (甘肅蘭州 730030);

目的  觀察N-乙酰半胱氨酸 (NAC) 對重癥急性胰腺炎 (SAP) 大鼠腸屏障功能的保護作用及其可能機理。
方法  將80只Wistar大鼠隨機 (隨機數(shù)字表法) 分為正常對照組 (CON組,n=8)、假手術(shù)組 (SO組,n=24)、SAP組 (n=24) 及NAC組 (n=24),后3組再隨機 (隨機數(shù)字表法) 分為6、12及24h3個時間點組,每個時間點組8只大鼠。通過胰膽管逆行注射5%?;悄懰徕c的方法制作大鼠SAP模型,SO組大鼠則通過胰膽管逆行注射生理鹽水。NAC組大鼠于造模前1h經(jīng)腹腔注射NAC,而SO組和SAP組大鼠于相應(yīng)時間點經(jīng)腹腔注射生理鹽水。CON組大鼠不做任何處理,麻醉后直接取右心室血5mL及回腸組織約5cm,余3組大鼠則于術(shù)后6、12及24 h麻醉后取材。檢測血漿淀粉酶 (AMY)、C-反應(yīng)蛋白 (CRP)、內(nèi)毒素、D-乳酸及二胺氧化酶 (DAO) 含量;檢測回腸組織總超氧化物歧化酶 (T-SOD)、髓過氧化物酶 (MPO) 及丙二醛 (MDA) 含量;觀察回腸上皮細胞的凋亡情況、回腸組織的病理學(xué)改變并對其進行評分;檢測回腸組織bax和bcl-2mRNA及其蛋白的表達水平。
結(jié)果  與同時相SAP組比較,NAC組大鼠各時相的血漿CRP水平均較低 (P<0.05),而AMY水平在12h和24h時較低(P<0.05);NAC組大鼠的DAO、內(nèi)毒素及D-乳酸水平在12h和24h時均較低 (P<0.05),但DAO水平在6h時高于SAP組 (P<0.05);NAC組大鼠各時相回腸組織中的MPO及MDA水平均較低 (P<0.05),而T-SOD水平則在12h和24h時較高(P<0.05);NAC組大鼠回腸上皮細胞的凋亡指數(shù)均較低 (P<0.01),組織病理學(xué)評分在12h及24h時亦較低 (P<0.05);NAC組大鼠回腸組織中bax mRNA及其蛋白的表達水平均較低 (P<0.05),而bcl-2 mRNA及其蛋白的表達水平則均較高 (P<0.05)。
結(jié)論  NAC對SAP大鼠的腸屏障功能具有保護作用,其機理除了抗氧化作用外,還可能與其抗凋亡作用有關(guān)。

引用本文: 王映珍,牛天平,曹云華,王軍,李自力,肖文,張有成,王世文. N-乙酰半胱氨酸對重癥急性胰腺炎大鼠腸屏障保護作用機理的實驗研究△. 中國普外基礎(chǔ)與臨床雜志, 2013, 20(3): 271-279. doi: 復(fù)制

1. 孫備, 董承剛, 王剛, 等. 重癥急性胰腺炎死亡的高危因素分析[J]. 中華外科雜志, 2007, 45(23):1619-1622.
2. 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(chǔ)與臨床雜志, 2010, 17(10):1107-1108.
3. 閆堃, 黎一鳴, 紀宗正, 等. 緩釋泵法制備急性胰腺炎大鼠模型[J]. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(7):717-721.
4. Tayman C, Tonbul A, Kosus A, et al. N-acetylcysteine may preventsevere intestinal damage in necrotizing enterocolitis[J]. J PediatrSurg, 2012, 47(3):540-550.
5. Takatsuka S, Morita T, Horikiri Y, et al. Absorption enhancement of poorly absorbed hydrophilic compounds from various mucosal sites by combination of mucolytic agent and non-ionic surfactant[J]. Int J Pharm, 2007, 338(1-2):87-93.
6. Johnson ST, Bigam DL, Emara M, et al. Effects of N-acetylcysteine on intestinal reoxygenation injury in hypoxic newborn piglets resuscitated with 100% oxygen[J]. Neonatology, 2009, 96(3):162-170.
7. Oz S, Okay E, Karadenizli A, et al. N-acetylcysteine improves intestinal barrier in partially hepatectomized rats[J]. ANZ J Surg, 2007, 77(3):173-176.
8. 鄒忠東, 張再重, 王瑜, 等. N-乙酰半胱氨酸對重癥急性胰腺炎大鼠腸道屏障功能障礙與二次打擊的保護作用[J]. 中華實驗外科雜志, 2009, 26(1):64-66.
9. 黎君友, 于燕, 郝軍, 等. 分光光度法測定血和小腸組織二胺氧化酶活性[J]. 氨基酸和生物資源, 1996, 18(4):28-30.
10. Chiu CJ, Mcardle AH, Brown R, et al. Intestinal mucosal lesionin low-flow states. Ⅰ. A morphological, hemodynamic, and meta-bolic reappraisal[J]. Arch Surg, 1970, 101(4):478-483.
11. Leveau P, Wang X, Sun Z, et al. Severity of pancreatitis-associated gut barrier dysfunction is reduced following treatment with the PAF inhibitor lexipafant[J]. Biochem Pharmacol, 2005, 69(9):1325-1331.
12. 王強, 王湘英, 黃碩, 等. 重癥急性胰腺炎大鼠胃腸動力障礙機理的實驗研究[J]. 中國普外基礎(chǔ)與臨床雜志, 2012, 19(4):419-423.
13. 李奇智, 吳新民, 郭亞民. 相關(guān)細胞因子在重癥急性胰腺炎相關(guān)肺損傷中的作用[J]. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(3):258-260.
14. Zayat M, Lichtenberger LM, Dial EJ. Pathophysiology of LPS-induced gastrointestinal injury in the rat:role of secretory phospholipase A2[J]. Shock, 2008, 30(2):206-211.
15. Peng Y, Gallagher SF, Landmann R, et al. The role of p65NF-kappaB/RelA in pancreatitis-induced Kupffer cell apoptosis[J]. J Gastrointest Surg, 2006, 10(6):837-847.
16. 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.
17. Tadao M, Yuji O. Role of free radicals in the development of severe acute pancreatitis[J]. Nippon Rinsho, 2004, 62(11):2015-2020.
18. Sha H, Ma Q, Jha RK. Trypsin is the culprit of multiple organ injury with severe acute pancreatitis[J]. Med Hypotheses, 2009, 72(2):180-182.
19. Dryden GW Jr, Deaciuc I, Arteel G, et al. Clinical implications of oxidative stress and antioxidant therapy[J]. Curr Gastroenterol Rep, 2005, 7(4):308-316.
20. Czakó L, Hegyi P, Takács T, et al. Effects of octreotide on acute necrotizing pancreatitis in rabbits[J]. World J Gastroenterol, 2004, 10(14):2082-2086.
21. Telek G, Regöly-Mérei J, Kovács GC, et al. The first histologicaldemonstration of pancreatic oxidative stress in human acutepancreatitis[J]. Hepatogastroenterology, 2001, 48(41):1252-1258.
22. Sevillano S, De la Mano AM, De dios I, et al. Major pathologicalmechanisms of acute pancreatitis are prevented by N-acetylcysteine[J]. Digestion, 2003, 68(1):34-40.
23. Sevillano S, De la Mano AM, Manso MA, et al. N-acetylcysteine prevents intra-acinar oxygen free radical production in pancreatic duct obstruction-induced acute pancreatitis[J]. Biochim BiophysActa, 2003, 1639(3):177-184.
24. Xu GF, Lu Z, Gao J, et al. Effect of ecoimmunonutrition supportson maintenance of integrity of intestinal mucosal barrier in severe acute pancreatitis in dogs[J]. Chin Med J (Engl), 2006, 119(8):656-661.
25. Abu-Hilal M, Mcphail MJ, Marchand L, et al. Malondialdehyde and superoxide dismutase as potential markers of severity in acute pancreatitis[J]. JOP, 2006, 7(2):185-192.
26. Park BK, Chung JB, Lee JH, et al. Role of oxygen free radicals in patients with acute pancreatitis[J]. World J Gastroenterol, 2003, 9(10):2266-2269.
27. Baregamian N, Song J, Jeschke MG, et al. IGF-1 protects intestinalepithelial cells from oxidative stress-induced apoptosis[J]. J Surg Res, 2006, 136(1):31-37.
  1. 1. 孫備, 董承剛, 王剛, 等. 重癥急性胰腺炎死亡的高危因素分析[J]. 中華外科雜志, 2007, 45(23):1619-1622.
  2. 2. 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(chǔ)與臨床雜志, 2010, 17(10):1107-1108.
  3. 3. 閆堃, 黎一鳴, 紀宗正, 等. 緩釋泵法制備急性胰腺炎大鼠模型[J]. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(7):717-721.
  4. 4. Tayman C, Tonbul A, Kosus A, et al. N-acetylcysteine may preventsevere intestinal damage in necrotizing enterocolitis[J]. J PediatrSurg, 2012, 47(3):540-550.
  5. 5. Takatsuka S, Morita T, Horikiri Y, et al. Absorption enhancement of poorly absorbed hydrophilic compounds from various mucosal sites by combination of mucolytic agent and non-ionic surfactant[J]. Int J Pharm, 2007, 338(1-2):87-93.
  6. 6. Johnson ST, Bigam DL, Emara M, et al. Effects of N-acetylcysteine on intestinal reoxygenation injury in hypoxic newborn piglets resuscitated with 100% oxygen[J]. Neonatology, 2009, 96(3):162-170.
  7. 7. Oz S, Okay E, Karadenizli A, et al. N-acetylcysteine improves intestinal barrier in partially hepatectomized rats[J]. ANZ J Surg, 2007, 77(3):173-176.
  8. 8. 鄒忠東, 張再重, 王瑜, 等. N-乙酰半胱氨酸對重癥急性胰腺炎大鼠腸道屏障功能障礙與二次打擊的保護作用[J]. 中華實驗外科雜志, 2009, 26(1):64-66.
  9. 9. 黎君友, 于燕, 郝軍, 等. 分光光度法測定血和小腸組織二胺氧化酶活性[J]. 氨基酸和生物資源, 1996, 18(4):28-30.
  10. 10. Chiu CJ, Mcardle AH, Brown R, et al. Intestinal mucosal lesionin low-flow states. Ⅰ. A morphological, hemodynamic, and meta-bolic reappraisal[J]. Arch Surg, 1970, 101(4):478-483.
  11. 11. Leveau P, Wang X, Sun Z, et al. Severity of pancreatitis-associated gut barrier dysfunction is reduced following treatment with the PAF inhibitor lexipafant[J]. Biochem Pharmacol, 2005, 69(9):1325-1331.
  12. 12. 王強, 王湘英, 黃碩, 等. 重癥急性胰腺炎大鼠胃腸動力障礙機理的實驗研究[J]. 中國普外基礎(chǔ)與臨床雜志, 2012, 19(4):419-423.
  13. 13. 李奇智, 吳新民, 郭亞民. 相關(guān)細胞因子在重癥急性胰腺炎相關(guān)肺損傷中的作用[J]. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(3):258-260.
  14. 14. Zayat M, Lichtenberger LM, Dial EJ. Pathophysiology of LPS-induced gastrointestinal injury in the rat:role of secretory phospholipase A2[J]. Shock, 2008, 30(2):206-211.
  15. 15. Peng Y, Gallagher SF, Landmann R, et al. The role of p65NF-kappaB/RelA in pancreatitis-induced Kupffer cell apoptosis[J]. J Gastrointest Surg, 2006, 10(6):837-847.
  16. 16. 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.
  17. 17. Tadao M, Yuji O. Role of free radicals in the development of severe acute pancreatitis[J]. Nippon Rinsho, 2004, 62(11):2015-2020.
  18. 18. Sha H, Ma Q, Jha RK. Trypsin is the culprit of multiple organ injury with severe acute pancreatitis[J]. Med Hypotheses, 2009, 72(2):180-182.
  19. 19. Dryden GW Jr, Deaciuc I, Arteel G, et al. Clinical implications of oxidative stress and antioxidant therapy[J]. Curr Gastroenterol Rep, 2005, 7(4):308-316.
  20. 20. Czakó L, Hegyi P, Takács T, et al. Effects of octreotide on acute necrotizing pancreatitis in rabbits[J]. World J Gastroenterol, 2004, 10(14):2082-2086.
  21. 21. Telek G, Regöly-Mérei J, Kovács GC, et al. The first histologicaldemonstration of pancreatic oxidative stress in human acutepancreatitis[J]. Hepatogastroenterology, 2001, 48(41):1252-1258.
  22. 22. Sevillano S, De la Mano AM, De dios I, et al. Major pathologicalmechanisms of acute pancreatitis are prevented by N-acetylcysteine[J]. Digestion, 2003, 68(1):34-40.
  23. 23. Sevillano S, De la Mano AM, Manso MA, et al. N-acetylcysteine prevents intra-acinar oxygen free radical production in pancreatic duct obstruction-induced acute pancreatitis[J]. Biochim BiophysActa, 2003, 1639(3):177-184.
  24. 24. Xu GF, Lu Z, Gao J, et al. Effect of ecoimmunonutrition supportson maintenance of integrity of intestinal mucosal barrier in severe acute pancreatitis in dogs[J]. Chin Med J (Engl), 2006, 119(8):656-661.
  25. 25. Abu-Hilal M, Mcphail MJ, Marchand L, et al. Malondialdehyde and superoxide dismutase as potential markers of severity in acute pancreatitis[J]. JOP, 2006, 7(2):185-192.
  26. 26. Park BK, Chung JB, Lee JH, et al. Role of oxygen free radicals in patients with acute pancreatitis[J]. World J Gastroenterol, 2003, 9(10):2266-2269.
  27. 27. Baregamian N, Song J, Jeschke MG, et al. IGF-1 protects intestinalepithelial cells from oxidative stress-induced apoptosis[J]. J Surg Res, 2006, 136(1):31-37.
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