• 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(xué)院基礎(chǔ)醫(yī)學(xué)院(成都 610083);

目的 觀察凋亡抑制因子人類細(xì)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(guò)程中的表達(dá)和定位情況,并探討其意義。
方法 利用原位雜交法分別對(duì)15只犬(實(shí)驗(yàn)組)膽管損傷后2、3、4、5、6個(gè)月及其配對(duì)的15只假手術(shù)組犬的吻合口組織中c-FLIP表達(dá)和定位情況進(jìn)行分析,計(jì)算每張切片的平均積分光密度值,分別比較c-FLIP在實(shí)驗(yàn)組及其配對(duì)的假手術(shù)組的膽道吻合口間質(zhì)組織與腺體組織中表達(dá)的差異。
結(jié)果 實(shí)驗(yàn)組各時(shí)相的間質(zhì)組織中c-FLIP均呈強(qiáng)陽(yáng)性表達(dá),以纖維細(xì)胞胞漿表達(dá)為主,而腺體組織很少表達(dá)或幾乎無(wú)表達(dá); 在相應(yīng)時(shí)相的間質(zhì)組織中的表達(dá)明顯強(qiáng)于在腺體組織中的表達(dá)(P lt;0.05); 間質(zhì)組織或腺體組織中c-FLIP表達(dá)在不同時(shí)相之間差異均無(wú)統(tǒng)計(jì)學(xué)意義(P gt;0.05)。假手術(shù)組各時(shí)相的間質(zhì)組織和腺體組織中c-FLIP均呈弱陽(yáng)性表達(dá); 在相應(yīng)時(shí)相的間質(zhì)組織和腺體組織中c-FLIP表達(dá)差異無(wú)統(tǒng)計(jì)學(xué)意義(P gt;0.05); 間質(zhì)組織或腺體組織中c-FLIP表達(dá)在不同時(shí)相之間差異均無(wú)統(tǒng)計(jì)學(xué)意義(P gt;0.05)。c-FLIP在實(shí)驗(yàn)組間質(zhì)組織中的表達(dá)明顯強(qiáng)于相應(yīng)時(shí)相的假手術(shù)組(P lt;0.05); 而c-FLIP在腺體組織中的表達(dá)2組間差異無(wú)統(tǒng)計(jì)學(xué)意義(P gt;0.05)。
結(jié)論 膽管損傷后,吻合口間質(zhì)組織內(nèi)的c-FLIP呈持續(xù)表達(dá)狀態(tài),由此所造成的細(xì)胞凋亡持續(xù)受阻效應(yīng)可能與膽管良性狹窄的形成關(guān)系密切。

引用本文： 駱樂(lè),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(guò)程中c-FLIP的表達(dá)及意義. 中國(guó)普外基礎(chǔ)與臨床雜志, 2010, 17(3): 253-257. doi: 復(fù)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(guò)程中顯微結(jié)構(gòu)和超微結(jié)構(gòu)的變化 [J]. 第四軍醫(yī)大學(xué)學(xué)報(bào), 2002; 23(16): 14971500.
3. 耿智敏, 向國(guó)安, 韓慶, 等. 轉(zhuǎn)化生長(zhǎng)因子β1 在膽管愈合過(guò)程中的表達(dá)及意義 [J]. 中國(guó)普外基礎(chǔ)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(dá)及相關(guān)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(dá)及意義 [J]. 中國(guó)普外基礎(chǔ)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(dǎo)犬膽管增殖平滑肌細(xì)胞凋亡與防治膽管狹窄關(guān)系研究 [J]. 中國(guó)普外基礎(chǔ)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(guò)程中顯微結(jié)構(gòu)和超微結(jié)構(gòu)的變化 [J]. 第四軍醫(yī)大學(xué)學(xué)報(bào), 2002; 23(16): 14971500.
  3. 3. 耿智敏, 向國(guó)安, 韓慶, 等. 轉(zhuǎn)化生長(zhǎng)因子β1 在膽管愈合過(guò)程中的表達(dá)及意義 [J]. 中國(guó)普外基礎(chǔ)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(dá)及相關(guān)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(dá)及意義 [J]. 中國(guó)普外基礎(chǔ)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(dǎo)犬膽管增殖平滑肌細(xì)胞凋亡與防治膽管狹窄關(guān)系研究 [J]. 中國(guó)普外基礎(chǔ)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.