• 1.西安交通大學醫(yī)學院肝膽外科(陜西西安 710061);;
  • 2.湖北醫(yī)藥學院附屬人民醫(yī)院甲狀腺乳腺血管外科(湖北十堰 442000);

目的探討前列腺素F2α受體(PTGFR)和前列腺素合酶2(COX-2)在膽管良性瘢痕組織中的表達及意義，并研究轉化生長因子-β1(TGF-β1)對膽管成纖維細胞中PTGFR表達的影響。方法收集2008～2010年西安交通大學第一附屬醫(yī)院肝膽外科收治的18例肝外膽管瘢痕性狹窄患者的膽總管組織，另收集6例來自異體肝移植供體的正常膽總管組織作為對照。采用免疫組織化學SABC法分別檢測PTGFR及COX-2在兩種組織中的表達情況，然后用不同濃度(0、10、20及30 ng/ml) TGF-β1作用于膽管成纖維細胞后24 h，用半定量RT-PCR法以及ELISA法檢測膽管成纖維細胞中PTGFR的mRNA及蛋白表達。結果PTGFR和COX-2在膽管良性瘢痕組織中的表達陽性率分別為88.9%(16/18)和83.3%(15/18)，正常膽總管組織中其表達陽性率分別為33.3%(2/6)及0(0/6)，PTGFR及COX-2在前者均分別明顯高于后者(P lt;0.05)。TGF-β1作用于膽管成纖維細胞后24 h，隨著TGF-β1濃度增高，可上調PTGFR mRNA及蛋白在膽管成纖維細胞中的表達，并且呈濃度依賴性(P lt;0.05)。結論膽管良性瘢痕組織中PTGFR和COX-2高度表達是造成膽管瘢痕過度增生的重要因素，TGF-β1可誘導膽管成纖維細胞中PTGFR的表達增高，并呈濃度依賴性，調節(jié)膽管瘢痕的形成。

引用本文： 李常恩,姚英民,韓少山,劉萬濤,劉青光. 膽管良性瘢痕組織中前列腺素F2α受體及前列腺素合酶2的表達及意義. 中國普外基礎與臨床雜志, 2011, 18(12): 1283-1287. doi: 復制

1. Oga T, Matsuoka T, Yao C, et al. Prostaglandin F2α receptor signaling facilitates bleomycininduced pulmonary fibrosis independently of transforming growth factorβ [J]. Nat Med, 2009, 15: 14261430.
2. 耿智敏, 向國安, 韓慶, 等. 平滑肌肌動蛋白(SMA)在膽道愈合過程中的表達及意義 [J]. 肝膽外科雜志, 2000, 8(4): 312313.
3. 韓少山, 劉青光, 姚英民, 等. UbcH10在肝細胞癌中的表達及臨床病理意義 [J]. 南方醫(yī)科大學學報, 2011, 31(2): 280284.
4. Sváb J, Pesková M, Krska Z, et al. Prevention, diagnosis and treatment of iatrogennic lesions of biliary tract during laparoscopic cholecystectomy. Management of papila injury after invasive endoscopy. Part 1. Prevention and diagnosis of bile duct injuries [J]. Rozhl Chir, 2005, 84(4): 176181.
5. 黃志強. 膽管損傷: 肝膽外科永久的議題 [J]. 中華普通外科雜志, 2001, 16(6): 371373.
6. Geng ZM, Yao YM, Liu QG, et al. Mechanism of benign biliary stricture: a morphological and immunohistochemical study [J]. World J Gastroenterol, 2005, 11(2): 293295.
7. Prat F, Chapat O, Ducot B, et al. Predictive factors for survival of patients with inoperable malignant distal biliary strictures: a practical management guideline [J]. Gut, 1998, 42(1): 7680.
8. Sohn TA, Yeo CJ, Cameron JL, et al. Do preoperative biliary stents increase postpancreaticoduodenectomy complications? [J]. J Gastrointest Surg, 2000, 4(3): 258267.
9. 耿智敏, 向國安, 韓慶, 等. 巨噬細胞及轉化生長因子β1在肝外膽管損傷修復過程中的表達及其意義 [J]. 中華實驗外科雜志, 2000, 17(6): 522523.
10. 耿智敏, 劉青光, 潘承恩, 等. 肌成纖維細胞在膽道愈合過程中的表達及意義 [J]. 中華實驗外科雜志, 2001, 18(3): 205206.
11. 耿智敏, 徐軍, 劉青光, 等. 良性膽管狹窄形成機制的研究 [J]. 消化外科, 2002, 1(5): 321323.
12. 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.
13. Sales KJ, Milne SA, Williams AR, et al. Expression, localization, and signaling of prostaglandin F2α receptor in human endometrial adenocarcinoma: regulation of proliferation by activation of the epidermal growth factor receptor and mitogenactivated protein kinase signaling pathways [J]. J Clin Endocrinol Metab, 2004, 89(2): 986993.
14. Zaragoza DB, Wilson RR, Mitchell BF, et al. The interleukin 1βinduced expression of human prostaglandin F2α receptor messenger RNA in human myometrialderived ULTR cells requires the transcription factor, NFkappaB [J]. Biol Reprod, 2006, 75(5): 697704.
15. Olman MA. Beyond TGFβ: a prostaglandin promotes fibrosis [J]. Nat Med, 2009, 15(12): 13601361.
16. 梁君蓉, 王新, 吳開春, 等. COX2抑制劑對成纖維細胞的增殖和細胞外基質產生的影響 [J]. 第四軍醫(yī)大學學報, 2004, 25(9): 811814.
17. Jackson BA, Goldstein RH, Roy R, et al. Effects of transforming growth factor β and interleukin1β on expression of cyclooxygenase 1 and 2 and phospholipase A2 mRNA in lung fibroblasts and endothelial cells in culture [J]. Biochem Biophys Res Commun, 1993, 197(3): 14651474.
18. Luo J, Lang JA, Miller MW. Transforming growth factor β1 regulates the expression of cyclooxygenase in cultured cortical astrocytes and neurons [J]. J Neurochem, 1998, 71(2): 526534.
19. Fong CY, Pang L, Holland E, et al. TGFβ1 stimulates IL8 release, COX2 expression, and PGE2 release in human airway smooth muscle cells [J]. Am J Physiol Lung Cell Mol Physiol, 2000, 279(1): L201L207.
20. 張小文, 施國明, 鄒浩, 等. 良性膽管狹窄瘢痕中CD68、TGFβ1、αSMA的表達 [J]. 中華肝膽外科雜志, 2007, 13(11): 750753.
21. 謝舉臨, 利天增, 祁少海, 等. 轉化生長因子β1對培養(yǎng)的瘢痕成纖維細胞增殖的調控作用 [J]. 中國組織化學與細胞化學雜志, 2006, 15(1): 3033.
22. Wang R, Ghahary A, Shen Q, et al. Hypertrophic scar tissues and fibroblasts produce more transforming growth factorβ1 mRNA and protein than normal skin and cells [J]. Wound Repair Regen, 2000, 8(2): 128137.
23. Kwak HJ, Park MJ, Cho H, et al. Transforming growth factorβ1 induces tissue inhibitor of metalloproteinase1 expression via activation of extracellular signalregulated kinase and Sp1 in human fibrosarcoma cells [J]. Mol Cancer Res, 2006, 4(3): 209220.
24. Singh NN, Ramji DP. The role of transforming growth factorβ in atherosclerosis cytokine [J]. Growth Factor Rev, 2006, 17(06): 489499.
25. Nedelec B, Ghahary A, Scott PG, et al. Control of wound contraction. Basic and clinical features [J]. Hand Clin, 2000, 16(2): 289302.
26. Sumiyoshi K, Nakao A, Setoguchi Y, et al. Smads regulate collagen gel contraction by human dermal fibroblasts [J]. Br J Dermatol, 2003, 149(3): 464470.
  1. 1. Oga T, Matsuoka T, Yao C, et al. Prostaglandin F2α receptor signaling facilitates bleomycininduced pulmonary fibrosis independently of transforming growth factorβ [J]. Nat Med, 2009, 15: 14261430.
  2. 2. 耿智敏, 向國安, 韓慶, 等. 平滑肌肌動蛋白(SMA)在膽道愈合過程中的表達及意義 [J]. 肝膽外科雜志, 2000, 8(4): 312313.
  3. 3. 韓少山, 劉青光, 姚英民, 等. UbcH10在肝細胞癌中的表達及臨床病理意義 [J]. 南方醫(yī)科大學學報, 2011, 31(2): 280284.
  4. 4. Sváb J, Pesková M, Krska Z, et al. Prevention, diagnosis and treatment of iatrogennic lesions of biliary tract during laparoscopic cholecystectomy. Management of papila injury after invasive endoscopy. Part 1. Prevention and diagnosis of bile duct injuries [J]. Rozhl Chir, 2005, 84(4): 176181.
  5. 5. 黃志強. 膽管損傷: 肝膽外科永久的議題 [J]. 中華普通外科雜志, 2001, 16(6): 371373.
  6. 6. Geng ZM, Yao YM, Liu QG, et al. Mechanism of benign biliary stricture: a morphological and immunohistochemical study [J]. World J Gastroenterol, 2005, 11(2): 293295.
  7. 7. Prat F, Chapat O, Ducot B, et al. Predictive factors for survival of patients with inoperable malignant distal biliary strictures: a practical management guideline [J]. Gut, 1998, 42(1): 7680.
  8. 8. Sohn TA, Yeo CJ, Cameron JL, et al. Do preoperative biliary stents increase postpancreaticoduodenectomy complications? [J]. J Gastrointest Surg, 2000, 4(3): 258267.
  9. 9. 耿智敏, 向國安, 韓慶, 等. 巨噬細胞及轉化生長因子β1在肝外膽管損傷修復過程中的表達及其意義 [J]. 中華實驗外科雜志, 2000, 17(6): 522523.
  10. 10. 耿智敏, 劉青光, 潘承恩, 等. 肌成纖維細胞在膽道愈合過程中的表達及意義 [J]. 中華實驗外科雜志, 2001, 18(3): 205206.
  11. 11. 耿智敏, 徐軍, 劉青光, 等. 良性膽管狹窄形成機制的研究 [J]. 消化外科, 2002, 1(5): 321323.
  12. 12. 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.
  13. 13. Sales KJ, Milne SA, Williams AR, et al. Expression, localization, and signaling of prostaglandin F2α receptor in human endometrial adenocarcinoma: regulation of proliferation by activation of the epidermal growth factor receptor and mitogenactivated protein kinase signaling pathways [J]. J Clin Endocrinol Metab, 2004, 89(2): 986993.
  14. 14. Zaragoza DB, Wilson RR, Mitchell BF, et al. The interleukin 1βinduced expression of human prostaglandin F2α receptor messenger RNA in human myometrialderived ULTR cells requires the transcription factor, NFkappaB [J]. Biol Reprod, 2006, 75(5): 697704.
  15. 15. Olman MA. Beyond TGFβ: a prostaglandin promotes fibrosis [J]. Nat Med, 2009, 15(12): 13601361.
  16. 16. 梁君蓉, 王新, 吳開春, 等. COX2抑制劑對成纖維細胞的增殖和細胞外基質產生的影響 [J]. 第四軍醫(yī)大學學報, 2004, 25(9): 811814.
  17. 17. Jackson BA, Goldstein RH, Roy R, et al. Effects of transforming growth factor β and interleukin1β on expression of cyclooxygenase 1 and 2 and phospholipase A2 mRNA in lung fibroblasts and endothelial cells in culture [J]. Biochem Biophys Res Commun, 1993, 197(3): 14651474.
  18. 18. Luo J, Lang JA, Miller MW. Transforming growth factor β1 regulates the expression of cyclooxygenase in cultured cortical astrocytes and neurons [J]. J Neurochem, 1998, 71(2): 526534.
  19. 19. Fong CY, Pang L, Holland E, et al. TGFβ1 stimulates IL8 release, COX2 expression, and PGE2 release in human airway smooth muscle cells [J]. Am J Physiol Lung Cell Mol Physiol, 2000, 279(1): L201L207.
  20. 20. 張小文, 施國明, 鄒浩, 等. 良性膽管狹窄瘢痕中CD68、TGFβ1、αSMA的表達 [J]. 中華肝膽外科雜志, 2007, 13(11): 750753.
  21. 21. 謝舉臨, 利天增, 祁少海, 等. 轉化生長因子β1對培養(yǎng)的瘢痕成纖維細胞增殖的調控作用 [J]. 中國組織化學與細胞化學雜志, 2006, 15(1): 3033.
  22. 22. Wang R, Ghahary A, Shen Q, et al. Hypertrophic scar tissues and fibroblasts produce more transforming growth factorβ1 mRNA and protein than normal skin and cells [J]. Wound Repair Regen, 2000, 8(2): 128137.
  23. 23. Kwak HJ, Park MJ, Cho H, et al. Transforming growth factorβ1 induces tissue inhibitor of metalloproteinase1 expression via activation of extracellular signalregulated kinase and Sp1 in human fibrosarcoma cells [J]. Mol Cancer Res, 2006, 4(3): 209220.
  24. 24. Singh NN, Ramji DP. The role of transforming growth factorβ in atherosclerosis cytokine [J]. Growth Factor Rev, 2006, 17(06): 489499.
  25. 25. Nedelec B, Ghahary A, Scott PG, et al. Control of wound contraction. Basic and clinical features [J]. Hand Clin, 2000, 16(2): 289302.
  26. 26. Sumiyoshi K, Nakao A, Setoguchi Y, et al. Smads regulate collagen gel contraction by human dermal fibroblasts [J]. Br J Dermatol, 2003, 149(3): 464470.