• 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(duì)重癥急性胰腺炎 (SAP) 大鼠腸屏障功能的保護(hù)作用及其可能機(jī)理。
方法  將80只Wistar大鼠隨機(jī) (隨機(jī)數(shù)字表法) 分為正常對(duì)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(jī) (隨機(jī)數(shù)字表法) 分為6、12及24h3個(gè)時(shí)間點(diǎn)組,每個(gè)時(shí)間點(diǎn)組8只大鼠。通過(guò)胰膽管逆行注射5%牛磺膽酸鈉的方法制作大鼠SAP模型,SO組大鼠則通過(guò)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(shí)間點(diǎn)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(cè)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(cè)回腸組織總超氧化物歧化酶 (T-SOD)、髓過(guò)氧化物酶 (MPO) 及丙二醛 (MDA) 含量;觀察回腸上皮細(xì)胞的凋亡情況、回腸組織的病理學(xué)改變并對(duì)其進(jìn)行評(píng)分;檢測(cè)回腸組織bax和bcl-2mRNA及其蛋白的表達(dá)水平。
結(jié)果  與同時(shí)相SAP組比較,NAC組大鼠各時(shí)相的血漿CRP水平均較低 (P<0.05),而AMY水平在12h和24h時(shí)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(shí)均較低 (P<0.05),但DAO水平在6h時(shí)高于SAP組 (P<0.05);NAC組大鼠各時(shí)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(shí)較高(P<0.05);NAC組大鼠回腸上皮細(xì)胞的凋亡指數(shù)均較低 (P<0.01),組織病理學(xué)評(píng)分在12h及24h時(shí)亦較低 (P<0.05);NAC組大鼠回腸組織中bax mRNA及其蛋白的表達(dá)水平均較低 (P<0.05),而bcl-2 mRNA及其蛋白的表達(dá)水平則均較高 (P<0.05)。
結(jié)論  NAC對(duì)SAP大鼠的腸屏障功能具有保護(hù)作用,其機(jī)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(duì)重癥急性胰腺炎大鼠腸屏障保護(hù)作用機(jī)理的實(shí)驗(yàn)研究△. 中國(guó)普外基礎(chǔ)與臨床雜志, 2013, 20(3): 271-279. doi: 復(fù)制

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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(jiàn)并發(fā)癥及防治[J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2010, 17(10):1107-1108.
3. 閆堃, 黎一鳴, 紀(jì)宗正, 等. 緩釋泵法制備急性胰腺炎大鼠模型[J]. 中國(guó)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?jiān)僦兀?王瑜, 等. N-乙酰半胱氨酸對(duì)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(hù)作用[J]. 中華實(shí)驗(yàn)外科雜志, 2009, 26(1):64-66.
9. 黎君友, 于燕, 郝軍, 等. 分光光度法測(cè)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(qiáng), 王湘英, 黃碩, 等. 重癥急性胰腺炎大鼠胃腸動(dòng)力障礙機(jī)理的實(shí)驗(yàn)研究[J]. 中國(guó)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(xì)胞因子在重癥急性胰腺炎相關(guān)肺損傷中的作用[J]. 中國(guó)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(jiàn)并發(fā)癥及防治[J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2010, 17(10):1107-1108.
  3. 3. 閆堃, 黎一鳴, 紀(jì)宗正, 等. 緩釋泵法制備急性胰腺炎大鼠模型[J]. 中國(guó)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?jiān)僦兀?王瑜, 等. N-乙酰半胱氨酸對(duì)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(hù)作用[J]. 中華實(shí)驗(yàn)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(cè)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(qiáng), 王湘英, 黃碩, 等. 重癥急性胰腺炎大鼠胃腸動(dòng)力障礙機(jī)理的實(shí)驗(yàn)研究[J]. 中國(guó)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(xì)胞因子在重癥急性胰腺炎相關(guān)肺損傷中的作用[J]. 中國(guó)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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