• 福建醫(yī)科大學(xué)附屬協(xié)和醫(yī)院普外科（福建福州 350001）;

目的研究緊密連接蛋白-1(ZO-1)在重癥急性胰腺炎(SAP)大鼠回腸組織中的表達(dá)情況，初步探討SAP時(shí)腸黏膜屏障損傷的可能機(jī)理。方法SD雄性大鼠50只，按完全隨機(jī)法分為假手術(shù)組和SAP組，SAP組按取材時(shí)間不同又分為3、6、12及24 h 4個(gè)亞組，每組10只。SAP組采用Aho法逆行穿刺膽胰管注射5%?；敲撗跄懰徕c建立SAP模型，分別于造模后第3、6、12及24 h處死大鼠，假手術(shù)組直接處死。建模成功后檢測(cè)腫瘤壞死因子-α(TNF-α)水平及二胺氧化酶(DAO)活性，同時(shí)觀察胰腺和回腸組織的病理改變，分別用免疫組織化學(xué)蛋白定位及逆轉(zhuǎn)錄聚合酶鏈反應(yīng)(RT-PCR)檢測(cè)回腸組織中ZO-1蛋白和mRNA表達(dá)水平。結(jié)果與假手術(shù)組〔TNF-α: (10.83±0.96) ng/L; DAO: (354.79±3.67) U/L; ZO-1 蛋白: (10.40±0.45)分; ZO-1 mRNA: 0.878±0.014 8〕相比較，SAP組制模后不同時(shí)相大鼠血清中TNF-α水平〔3 h: (125.30±0.94) ng/L; 6 h: (181.89±4.93) ng/L; 12 h: (230.58±1.28) ng/L; 24 h: (198.89±4.83) ng/L〕明顯升高(P lt;0.05)，血漿中DAO活性〔3 h: (235.77±0.67) U/L; 6 h: (117.22±5.58) U/L; 12 h: (106.69±1.39) U/L; 24 h: (91.18±1.09) U/L〕明顯降低(P lt;0.05)； 回腸組織中ZO-1 蛋白〔3 h: (8.70±0.22)分; 6 h: (3.73±0.19)分; 12 h: (3.92±0.22)分; 24 h: (4.29±0.30)分〕和mRNA(3 h: 0.806±0.020 7; 6 h: 0.370±0.015 8; 12 h: 0.502±0.019 2; 24 h: 0.562±0.030 3)表達(dá)明顯下調(diào)(P lt;0.05)； 同時(shí)胰腺組織及回腸黏膜絨毛上皮壞死、血管破裂出血、炎性細(xì)胞浸潤(rùn)。結(jié)論大鼠回腸組織中ZO-1 表達(dá)下調(diào)是SAP腸黏膜屏障損傷的重要原因之一，可能與炎性細(xì)胞因子TNF-α的過度釋放及DAO活性降低有關(guān)。

引用本文： 曹洪慶,黃鶴光,陳燕昌,李洪森. 重癥急性胰腺炎大鼠緊密連接蛋白-1的表達(dá)與腸黏膜屏障損傷. 中國(guó)普外基礎(chǔ)與臨床雜志, 2011, 18(3): 240-244. doi: 復(fù)制

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1. Ammori BJ. Gut barrier dysfunction in patients with acute pancreatitis [J]. J Hepatobiliary Pancreat Surg, 2002, 9(4): 411412．.
2. 楊雪菲, 王春友． 對(duì)重型急性胰腺炎的認(rèn)識(shí)現(xiàn)況 [J]． 中國(guó)綜合臨床， 2005, 21(1): 9596．.
3. Furuya T, Soeno T, Komatsu M． Strategy for bacterial translocation in acute pancreatitis [J]．Nippon Shokakibyo Gakkai Zasshi， 2004, 101(5)：502509．.
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. Soslow RA, Dannenberg AJ, Rush D, et al. COX2 is expressed in human pulmonary, colonic, and mammary tumors [J]. Cancer, 2000, 89(12): 26372645.
6. Nusrat A, Parkos CA, Verkade P, et al. Tight junctions are membrane microdomains [J]. J Cell Sci, 2000, 113 (Pt 10): 17711781．.
7. Khler K， Zahraoui A. Tight junction: a coordinator of cell signalling and membrane trafficking [J]. Biol Cell, 2005, 97(8): 659665.
8. 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．.
9. Sawada N, Murata M, Kikuchi K, et al. Tight junctions and human diseases [J]. Med Electron Microsc, 2003, 36(3): 147156．.
10. 高志光, 秦環(huán)龍. 腸上皮細(xì)胞緊密連接的生物學(xué)功能及在腸屏障中的作用 [J]. 腸外與腸內(nèi)營(yíng)養(yǎng)， 2005, 12(5): 299302．.
11. 鮑歡, 包仕堯. 缺氧后血腦屏障緊密連接變化的分子機(jī)制 [J]. 國(guó)外醫(yī)學(xué)血管疾病分冊(cè), 2005, 13(8): 604608.
12. Umeda K, Matsui T, Nakayama M, et al. Establishment and characterization of cultured epithelial cells lacking expression of ZO1 [J]. J Biol Chem, 2004, 279(43): 4478544794．.
13. Youakim A, Ahdieh M. Interferongamma decreases barrier function in T84 cells by reducing ZO1 levels and disrupting apical actin [J]. Am J Physiol, 1999, 276(5 Pt 1): G1279G1288.
14. Weiler F, Marbe T, Scheppach W, et al. Influence of protein kinase C on transcription of the tight junction elements ZO1 and occludin [J]. J Cell Physiol, 2005, 204(1): 8386.
15. Cario E, Gerken G, Podolsky DK. Tolllike receptor 2 enhances ZO1associated intestinal epithelial barrier integrity via protein kinase C [J]. Gastroenterology, 2004, 127(1): 224238.
16. 楊植, 楊志英, 唐偉松, 等. 腫瘤壞死因子在猴急性胰腺炎中的作用及生長(zhǎng)抑素的治療效果 [J]．普外基礎(chǔ)與臨床雜志，1996, 3(1): 46．.
17. 王昌成, 馬興剛, 徐淮, 等. 血清IL6、IL8和TNFα在早期診斷重癥急性胰腺炎中的價(jià)值 [J]. 中華急診醫(yī)學(xué)雜志, 2001, 10(4): 252253.
18. Blikslager AT, Moeser AJ, Gookin JL, et al. Restoration of barrier function in injured intestinal mucosa [J]. Physiol Rev, 2007, 87(2): 545564．.
19. Li Q, Zhang Q, Wang M, et al. Interferongamma and tumor necrosis factoralpha disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction [J]. Clin Immunol, 2008, 126(1): 6780．.
20. 黎君友, 呂藝, 付小兵, 等. 二胺氧化酶在創(chuàng)傷后腸道損傷中變化及意義 [J]．中國(guó)危重病急救醫(yī)學(xué), 2000, 12(8): 482484．.
  1. 1. Ammori BJ. Gut barrier dysfunction in patients with acute pancreatitis [J]. J Hepatobiliary Pancreat Surg, 2002, 9(4): 411412．.
  2. 2. 楊雪菲, 王春友． 對(duì)重型急性胰腺炎的認(rèn)識(shí)現(xiàn)況 [J]． 中國(guó)綜合臨床， 2005, 21(1): 9596．.
  3. 3. Furuya T, Soeno T, Komatsu M． Strategy for bacterial translocation in acute pancreatitis [J]．Nippon Shokakibyo Gakkai Zasshi， 2004, 101(5)：502509．.
  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. Soslow RA, Dannenberg AJ, Rush D, et al. COX2 is expressed in human pulmonary, colonic, and mammary tumors [J]. Cancer, 2000, 89(12): 26372645.
  6. 6. Nusrat A, Parkos CA, Verkade P, et al. Tight junctions are membrane microdomains [J]. J Cell Sci, 2000, 113 (Pt 10): 17711781．.
  7. 7. Khler K， Zahraoui A. Tight junction: a coordinator of cell signalling and membrane trafficking [J]. Biol Cell, 2005, 97(8): 659665.
  8. 8. 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．.
  9. 9. Sawada N, Murata M, Kikuchi K, et al. Tight junctions and human diseases [J]. Med Electron Microsc, 2003, 36(3): 147156．.
  10. 10. 高志光, 秦環(huán)龍. 腸上皮細(xì)胞緊密連接的生物學(xué)功能及在腸屏障中的作用 [J]. 腸外與腸內(nèi)營(yíng)養(yǎng)， 2005, 12(5): 299302．.
  11. 11. 鮑歡, 包仕堯. 缺氧后血腦屏障緊密連接變化的分子機(jī)制 [J]. 國(guó)外醫(yī)學(xué)血管疾病分冊(cè), 2005, 13(8): 604608.
  12. 12. Umeda K, Matsui T, Nakayama M, et al. Establishment and characterization of cultured epithelial cells lacking expression of ZO1 [J]. J Biol Chem, 2004, 279(43): 4478544794．.
  13. 13. Youakim A, Ahdieh M. Interferongamma decreases barrier function in T84 cells by reducing ZO1 levels and disrupting apical actin [J]. Am J Physiol, 1999, 276(5 Pt 1): G1279G1288.
  14. 14. Weiler F, Marbe T, Scheppach W, et al. Influence of protein kinase C on transcription of the tight junction elements ZO1 and occludin [J]. J Cell Physiol, 2005, 204(1): 8386.
  15. 15. Cario E, Gerken G, Podolsky DK. Tolllike receptor 2 enhances ZO1associated intestinal epithelial barrier integrity via protein kinase C [J]. Gastroenterology, 2004, 127(1): 224238.
  16. 16. 楊植, 楊志英, 唐偉松, 等. 腫瘤壞死因子在猴急性胰腺炎中的作用及生長(zhǎng)抑素的治療效果 [J]．普外基礎(chǔ)與臨床雜志，1996, 3(1): 46．.
  17. 17. 王昌成, 馬興剛, 徐淮, 等. 血清IL6、IL8和TNFα在早期診斷重癥急性胰腺炎中的價(jià)值 [J]. 中華急診醫(yī)學(xué)雜志, 2001, 10(4): 252253.
  18. 18. Blikslager AT, Moeser AJ, Gookin JL, et al. Restoration of barrier function in injured intestinal mucosa [J]. Physiol Rev, 2007, 87(2): 545564．.
  19. 19. Li Q, Zhang Q, Wang M, et al. Interferongamma and tumor necrosis factoralpha disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction [J]. Clin Immunol, 2008, 126(1): 6780．.
  20. 20. 黎君友, 呂藝, 付小兵, 等. 二胺氧化酶在創(chuàng)傷后腸道損傷中變化及意義 [J]．中國(guó)危重病急救醫(yī)學(xué), 2000, 12(8): 482484．.