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_《中國普外基礎與臨床雜志》

作者：

曹洪慶 , 黃鶴光 , 陳燕昌 , 李洪森

福建醫科大學附屬協和醫院普外科（福建福州 350001）;

關鍵詞：

重癥急性胰腺炎大鼠緊密連接蛋白-1 腸黏膜屏障

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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情況，初步探討SAP時腸黏膜屏障損傷的可能機理。方法SD雄性大鼠50只，按完全隨機法分為假手術組和SAP組，SAP組按取材時間不同又分為3、6、12及24 h 4個亞組，每組10只。SAP組采用Aho法逆行穿刺膽胰管注射5%牛磺脫氧膽酸鈉建立SAP模型，分別于造模后第3、6、12及24 h處死大鼠，假手術組直接處死。建模成功后檢測腫瘤壞死因子-α(TNF-α)水平及二胺氧化酶(DAO)活性，同時觀察胰腺和回腸組織的病理改變，分別用免疫組織化學蛋白定位及逆轉錄聚合酶鏈反應(RT-PCR)檢測回腸組織中ZO-1蛋白和mRNA表達水平。結果與假手術組〔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)表達明顯下調(P lt;0.05)；同時胰腺組織及回腸黏膜絨毛上皮壞死、血管破裂出血、炎性細胞浸潤。結論大鼠回腸組織中ZO-1 表達下調是SAP腸黏膜屏障損傷的重要原因之一，可能與炎性細胞因子TNF-α的過度釋放及DAO活性降低有關。

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的表達與腸黏膜屏障損傷. 中國普外基礎與臨床雜志, 2011, 18(3): 240-244. doi: 復制

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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抑素的治療效果 [J]．普外基礎與臨床雜志，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值 [J]. 中華急診醫學雜志, 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. 二胺氧化酶在創傷后腸道損傷中變化及意義 [J]．中國危重病急救醫學, 2000, 12(8): 482484．.

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．對重型急性胰腺炎的認識現況 [J]．中國綜合臨床， 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， 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制 [J]. 國外醫學血管疾病分冊, 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抑素的治療效果 [J]．普外基礎與臨床雜志，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值 [J]. 中華急診醫學雜志, 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. 二胺氧化酶在創傷后腸道損傷中變化及意義 [J]．中國危重病急救醫學, 2000, 12(8): 482484．.

《中國普外基礎與臨床雜志》

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

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《中國普外基礎與臨床雜志》

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

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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