• 1.成都軍區(qū)總醫(yī)院全軍腹部外科中心肝膽病區(qū)(成都 610083);;
  • 2.成都醫(yī)學院基礎醫(yī)學院(成都 610083);

目的 觀察凋亡抑制因子人類細胞同源FLICE樣抑制蛋白(cellular homolog FLICE-like inhibitory protein,c-FLIP)在膽管良性狹窄形成過程中的表達和定位情況,并探討其意義。
方法 利用原位雜交法分別對15只犬(實驗組)膽管損傷后2、3、4、5、6個月及其配對的15只假手術組犬的吻合口組織中c-FLIP表達和定位情況進行分析,計算每張切片的平均積分光密度值,分別比較c-FLIP在實驗組及其配對的假手術組的膽道吻合口間質組織與腺體組織中表達的差異。
結果 實驗組各時相的間質組織中c-FLIP均呈強陽性表達,以纖維細胞胞漿表達為主,而腺體組織很少表達或幾乎無表達; 在相應時相的間質組織中的表達明顯強于在腺體組織中的表達(P lt;0.05); 間質組織或腺體組織中c-FLIP表達在不同時相之間差異均無統(tǒng)計學意義(P gt;0.05)。假手術組各時相的間質組織和腺體組織中c-FLIP均呈弱陽性表達; 在相應時相的間質組織和腺體組織中c-FLIP表達差異無統(tǒng)計學意義(P gt;0.05); 間質組織或腺體組織中c-FLIP表達在不同時相之間差異均無統(tǒng)計學意義(P gt;0.05)。c-FLIP在實驗組間質組織中的表達明顯強于相應時相的假手術組(P lt;0.05); 而c-FLIP在腺體組織中的表達2組間差異無統(tǒng)計學意義(P gt;0.05)。
結論 膽管損傷后,吻合口間質組織內(nèi)的c-FLIP呈持續(xù)表達狀態(tài),由此所造成的細胞凋亡持續(xù)受阻效應可能與膽管良性狹窄的形成關系密切。

引用本文： 駱樂,李可洲,姚豫桐,閆洪濤,駱助林,榮成,張曉. 膽管損傷后良性狹窄形成過程中c-FLIP的表達及意義. 中國普外基礎與臨床雜志, 2010, 17(3): 253-257. doi: 復制

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1. Messadi DV, Le A, Berg S, et al. Expression of apoptosisassociated genes by human dermal scar fibroblasts [J]. Wound Repair Regen, 1999; 7(6): 511517.
2. 徐軍, 耿智敏, 劉青光, 等. 膽管損傷愈合過程中顯微結構和超微結構的變化 [J]. 第四軍醫(yī)大學學報, 2002; 23(16): 14971500.
3. 耿智敏, 向國安, 韓慶, 等. 轉化生長因子β1 在膽管愈合過程中的表達及意義 [J]. 中國普外基礎與臨床雜志, 2000; 7(6): 362363.
4. 張小文, 盧暉, 王琨, 等. 原癌基因蛋白CMYC和CFOS在良性膽道狹窄瘢痕組織中的表達及相關性研究 [J]. 云南醫(yī)藥, 2007; 28(2): 108110.
5. 高文超, 孫延平, 阮燦平, 等. cFLIP在大腸癌組織中的表達及意義 [J]. 中國普外基礎與臨床雜志, 2009; 12(3): 218222.
6. Djerbi M, DarrehShori T, Zhivotovsky B, et al. Characterization of the human FLICEinhibitory protein locus and comparison of the antiapoptotic activity of four different flip isoforms [J]. Scand J Immunol, 2001; 54(12): 180189.
7. Bodmer JL, Schrter M, Burns K, et al. Inhibition of death receptor signals by cellular FLIP [J]. Nature, 1997; 388(6638): 190195.
8. Ha JE, Choi YE, Jang J, et al. FLIP and MAPK play crucial roles in the MLN51mediated hyperproliferation of fibroblastlike synoviocytes in the pathogenesis of rheumatoid arthritis [J]. FEBS J, 2008; 275(14): 35463555.
9. Jiang T, Han Z, Chen S, et al. Resistance to activationinduced cell death and elevated FLIPL expression of CD4+ T cells in a polyI:Cinduced primary biliary cirrhosis mouse model [J]. Clin Exp Med， 2009; 9(4): 269276.
10. 何貴金, 高沁怡, 許書河, 等. 103鈀支架誘導犬膽管增殖平滑肌細胞凋亡與防治膽管狹窄關系研究 [J]. 中國普外基礎與臨床雜志, 2005; 12(4): 340342.
11. Yang JK. FLIP as an anticancer therapeutic target [J]. Yonsei Med J, 2008; 49(1): 1927.
12. Banno T, Gazel A, Blumenberg M. Pathwayspecific profiling identifies the NFkappa Bdependent tumor necrosis factor alpharegulated genes in epidermal keratinocytes [J]. J Biol Chem, 2005; 280(19): 1897318980.
13. Kreuz S, Siegmund D, Scheurich P, et al. NFκB inducers upregulate cFLIP, a cycloheximidesensitive inhibitor of death receptor signaling [J]. Mol Cell Biol, 2001; 21(12): 39643973.
14. Payne CM, Weber C, CrowleySkillicorn C, et al. Deoxycholate induces mitochondrial oxidative stress and activates NFkappaB through multiple mechanisms in HCT116 colon epithelial cells [J]. Carcinogenesis, 2007; 28(1): 215222.
15. Hirano F, Haneda M, Makino I. Chenodeoxycholic acid and taurochenodexycholic acid induce antiapoptotic cIAP1 expression in human hepatocytes [J]. J Gastroenterol Hepatol, 2006; 21(12): 18071813.
16. Alpini G, Glaser S, Alvaro D， et al. Bile acid depletion and repletion regulate cholangiocyte growth and secretion by a phosphatidylinositol 3kinasedependent pathway in rats [J]. Gastroenterology, 2002; 123(4): 12261237.
17. Xia X, Francis H, Glaser S, et al. Bile acid interactions with cholangiocytes [J]. World J Gastroenterol, 2006; 12(22): 35533563.
18. Lilienbaum A, Isral A. From calcium to NFkappa B signaling pathways in neurons [J]. Mol Cell Biol, 2003; 23(8): 26802698.
19. Pawar P, Ma L, Byon CH, et al. Molecular mechanisms of tamoxifen therapy for cholangiocarcinoma: role of calmodulin [J]. Clin Cancer Res, 2009; 15(4): 12881296.
  1. 1. Messadi DV, Le A, Berg S, et al. Expression of apoptosisassociated genes by human dermal scar fibroblasts [J]. Wound Repair Regen, 1999; 7(6): 511517.
  2. 2. 徐軍, 耿智敏, 劉青光, 等. 膽管損傷愈合過程中顯微結構和超微結構的變化 [J]. 第四軍醫(yī)大學學報, 2002; 23(16): 14971500.
  3. 3. 耿智敏, 向國安, 韓慶, 等. 轉化生長因子β1 在膽管愈合過程中的表達及意義 [J]. 中國普外基礎與臨床雜志, 2000; 7(6): 362363.
  4. 4. 張小文, 盧暉, 王琨, 等. 原癌基因蛋白CMYC和CFOS在良性膽道狹窄瘢痕組織中的表達及相關性研究 [J]. 云南醫(yī)藥, 2007; 28(2): 108110.
  5. 5. 高文超, 孫延平, 阮燦平, 等. cFLIP在大腸癌組織中的表達及意義 [J]. 中國普外基礎與臨床雜志, 2009; 12(3): 218222.
  6. 6. Djerbi M, DarrehShori T, Zhivotovsky B, et al. Characterization of the human FLICEinhibitory protein locus and comparison of the antiapoptotic activity of four different flip isoforms [J]. Scand J Immunol, 2001; 54(12): 180189.
  7. 7. Bodmer JL, Schrter M, Burns K, et al. Inhibition of death receptor signals by cellular FLIP [J]. Nature, 1997; 388(6638): 190195.
  8. 8. Ha JE, Choi YE, Jang J, et al. FLIP and MAPK play crucial roles in the MLN51mediated hyperproliferation of fibroblastlike synoviocytes in the pathogenesis of rheumatoid arthritis [J]. FEBS J, 2008; 275(14): 35463555.
  9. 9. Jiang T, Han Z, Chen S, et al. Resistance to activationinduced cell death and elevated FLIPL expression of CD4+ T cells in a polyI:Cinduced primary biliary cirrhosis mouse model [J]. Clin Exp Med， 2009; 9(4): 269276.
  10. 10. 何貴金, 高沁怡, 許書河, 等. 103鈀支架誘導犬膽管增殖平滑肌細胞凋亡與防治膽管狹窄關系研究 [J]. 中國普外基礎與臨床雜志, 2005; 12(4): 340342.
  11. 11. Yang JK. FLIP as an anticancer therapeutic target [J]. Yonsei Med J, 2008; 49(1): 1927.
  12. 12. Banno T, Gazel A, Blumenberg M. Pathwayspecific profiling identifies the NFkappa Bdependent tumor necrosis factor alpharegulated genes in epidermal keratinocytes [J]. J Biol Chem, 2005; 280(19): 1897318980.
  13. 13. Kreuz S, Siegmund D, Scheurich P, et al. NFκB inducers upregulate cFLIP, a cycloheximidesensitive inhibitor of death receptor signaling [J]. Mol Cell Biol, 2001; 21(12): 39643973.
  14. 14. Payne CM, Weber C, CrowleySkillicorn C, et al. Deoxycholate induces mitochondrial oxidative stress and activates NFkappaB through multiple mechanisms in HCT116 colon epithelial cells [J]. Carcinogenesis, 2007; 28(1): 215222.
  15. 15. Hirano F, Haneda M, Makino I. Chenodeoxycholic acid and taurochenodexycholic acid induce antiapoptotic cIAP1 expression in human hepatocytes [J]. J Gastroenterol Hepatol, 2006; 21(12): 18071813.
  16. 16. Alpini G, Glaser S, Alvaro D， et al. Bile acid depletion and repletion regulate cholangiocyte growth and secretion by a phosphatidylinositol 3kinasedependent pathway in rats [J]. Gastroenterology, 2002; 123(4): 12261237.
  17. 17. Xia X, Francis H, Glaser S, et al. Bile acid interactions with cholangiocytes [J]. World J Gastroenterol, 2006; 12(22): 35533563.
  18. 18. Lilienbaum A, Isral A. From calcium to NFkappa B signaling pathways in neurons [J]. Mol Cell Biol, 2003; 23(8): 26802698.
  19. 19. Pawar P, Ma L, Byon CH, et al. Molecular mechanisms of tamoxifen therapy for cholangiocarcinoma: role of calmodulin [J]. Clin Cancer Res, 2009; 15(4): 12881296.