肝切除聯合膽腸內引流對梗阻性黃疸大鼠的影響_《中國普外基礎與臨床雜志》

作者：

李斌 ¹ , 劉辰 ¹ , 易濱 ¹ , 羅祥基 ¹ , 高春芳 ² , 許強芝 ³ , 于勇 ¹ ,  姜小清 ¹

1.第二軍醫大學附屬東方肝膽外科醫院膽道一科(上海 200438);;
2.第二軍醫大學附屬東方肝膽外科醫院實驗診斷科(上海 200438);;
3.第二軍醫大學生化與分子生物學教研室(上海 200438);

關鍵詞：

梗阻性黃疸高膽紅素血癥肝切除膽道引流

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目的探索在高膽紅素血癥下，大鼠膽腸內引流聯合肝切除對肝功能、肝細胞能量代謝以及肝細胞再生和凋亡的影響。方法雄性成年SD大鼠120只，其中6只大鼠作為假手術(SO)組; 20只行70%肝切除，同時行膽總管-十二指腸插管橋接(70%PH組); 另94只行膽總管結扎(CBDL)制備梗阻性黃疸模型，建模成功后5 d時隨機取6只動物作為CBDL組，余下的動物5 d后行二次手術,再分為膽腸內引流再通組(BDORBF組，20只)、42%PH+BDORBF組(20只)及70%PH+BDORBF組(25只)。檢測CBDL組5 d時及二次手術后各組術后24 h、72 h及7 d時肝功能和肝細胞能量代謝、肝組織肝細胞生長因子(HGF)和bcl2 mRNA含量及其蛋白表達、肝細胞增殖指數和凋亡指數的變化。SO組只測定術后0 h肝功能和肝細胞能量指標。結果正常大鼠能夠耐受70%肝切除，術后肝細胞能量代謝和肝功能迅速恢復正常，肝再生良好、細胞凋亡無明顯增多。較之SO組和70%PH組，CBDL導致肝細胞能量代謝惡化、肝功能不良、肝組織HGF和bcl-2 mRNA含量減少，肝再生受抑制，細胞凋亡顯著增多(P lt;0.05)。膽腸內引流再通后肝細胞能量代謝可迅速恢復，肝細胞凋亡減少，肝再生活躍。42%+BDO-RBF組及70%PH+BDO-RBF組肝細胞能量代謝同樣能夠較快恢復，肝再生良好。42%+BDO-RBF組與70%PH+BDO-RBF組間各指標差異均無統計學意義(P gt;0.05)。結論梗阻性黃疸時，高膽紅素血癥嚴重影響肝細胞能量代謝和肝功能，引起肝細胞凋亡增多，肝再生受抑制; 及時有效的膽腸內引流能夠迅速改善肝細胞能量代謝、肝功能及肝再生，聯合肝切除時術前可不需常規膽道引流。

引用本文： 李斌,劉辰,易濱,羅祥基,高春芳,許強芝,于勇,姜小清. 肝切除聯合膽腸內引流對梗阻性黃疸大鼠的影響. 中國普外基礎與臨床雜志, 2011, 18(12): 1271-1277. doi: 復制

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5.	張永杰, 俞文隆, 黃立嵩, 等. 聯合肝葉切除及區域淋巴清掃治療肝門部膽管癌的初步觀察 [J]. 外科理論與實踐, 2005, 10(4): 323327.
6.	Kondo S, Hirano S, Ambo Y, et al. Forty consecutive resections of hilar cholangiocarcinoma with no postoperative mortality and no positive ductal margins: results of a prospective study [J]. Ann Surg, 2004, 240(1): 95101.
7.	Povoski SP, Karpeh MS Jr, Conlon KC, et al. Preoperative biliary drainage: impact on intraoperative bile cultures and infectious morbidity and mortality after pancreaticoduodenectomy [J]. J Gastrointest Surg, 1993, 3(5): 496505.
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.	Pisters PW, Hudec WA, Hess KR, et al. Effect of preoperative biliary decompression on pancreaticoduodenectomyassociated morbidity in 300 consecutive patients [J]. Ann Surg, 2001, 234(1): 4755.
10.	Martignoni ME, Wagner M, Krhenbühl L, et al. Effect of preoperative biliary drainage on surgical outcome after pancreatoduodenectomy [J]. Am J Surg, 2001, 181(1): 5259.
11.	Srivastava S, Sikora SS, Kumar A, et al. Outcome following pancreaticoduodenectomy in patients undergoing preoperative biliary drainage [J]. Dig Surg, 2001, 18(5): 381387.
12.	Sewnath ME, Karsten TM, Prins MH, et al. A metaanalysis on the efficacy of preoperative biliary drainage for tumors causing obstructive jaundice [J]. Ann Surg, 2002, 236(1): 1727.
13.	Cherqui D, Benoist S, Malassagne B, et al. Major liver resection for carcinoma in jaundiced patients without preoperative biliary drainage [J]. Arch Surg, 2000, 135(3): 302308.
14.	Mizuta A, Chijiiwa K, Saiki S, et al. Differences in biliary lipid excretion after major hepatectomy in obstructive jaundiced rats with preoperative internal, external, or no biliary drainage [J]. Eur Surg Res, 2002, 34(4): 291299.
15.	Sano T, Ajiki T, Takeyama Y, et al. Internal biliary drainage improves decreased number of gut mucosal T lymphocytes and MAdCAM1 expression in jaundiced rats [J]. Surgery, 2004, 136(3): 693699.
16.	Hayata A, Takeuchi E, Nagino M, et al. Hepatocyte growth factor concentration in rat bile is affected by hepatic resection volume and external biliary drainage [J]. J Surg Res, 1999, 85(1): 7176.
17.	Ueda J, Chijiiwa K, Nakano K, et al. Lack of intestinal bile results in delayed liver regeneration of normal rat liver after hepatectomy accompanied by impaired cyclin Eassociated kinase activity [J]. Surgery, 2002, 131(5): 564573.
18.	Zarnegar R, Michalopoulos GK. The many faces of hepatocyte growth factor: from hepatopoiesis to hematopoiesis [J]. J Cell Biol, 1995, 129(5): 11771180.
19.	Fausto N, Campbell JS, Riehle KJ. Liver regeneration [J]. Hepatology, 2006, 43(2 Suppl 1): S4553.
20.	Takushi Y, Shiraishi M, Nozato E, et al. Expression of antiapoptotic protein, Bcl2, in liver regeneration after a partial hepatectomy [J]. J Surg Res, 2006, 134(1): 93101.
21.	Yamamoto K, Morishita R, Hayashi S, et al. Contribution of Bcl2, but not BclxL and Bax, to antiapoptotic actions of hepatocyte growth factor in hypoxiaconditioned human endothelial cells [J]. Hypertension, 2001, 37(5): 13411348.
22.	韓德五. 肝功能不全//梁擴寰,李紹白. 肝臟病學 [M]. 第2版. 北京: 人民衛生出版社, 2003: 497513.
23.	Guerrieri F, Muolo L, Cocco T, et al. Correlation between rat liver regeneration and mitochondrial energy metabolism [J]. Biochim Biophys Acta, 1995, 1272(2): 95100.
24.	Hochwald SN, Burke EC, Jarnagin WR, et al. Association of preoperative biliary stenting with increased postoperative infectious complications in proximal cholangiocarcinoma [J]. Arch Surg, 1999, 134(3): 261266.
25.	Sakata J, Shirai Y, Wakai T, et al. Catheter tract implantation metastases associated with percutaneous biliary drainage for extrahepatic cholangiocarcinoma [J]. World J Gastroenterol, 2005, 11(44): 70247027.
26.	Seyama Y, Kubota K, Sano K, et al. Longterm outcome of extended hemihepatectomy for hilar bile duct Cancer with no mortality and high survival rate [J]. Ann Surg, 2003, 238(1): 7383.

1. Witzigmann H, Berr F, Ringel U, et al. Surgical and palliative management and outcome in 184 patients with hilar cholangiocarcinoma: palliative photodynamic therapy plus stenting is comparable to r1/r2 resection [J]. Ann Surg, 2006, 244(2): 230239.
2. Heimbach JK, Gores GJ, Haddock MG, et al. Predictors of disease recurrence following neoadjuvant chemoradiotherapy and liver transplantation for unresectable perihilar cholangiocarcinoma [J]. Transplantation, 2006, 82(12): 17031707.
3. Baton O, Azoulay D, Adam DV, et al. Major hepatectomy for hilar cholangiocarcinoma type 3 and 4: prognostic factors and longterm outcomes [J]. J Am Coll Surg, 2007, 204(2): 250260.
4. 程慶保, 張柏和, 張永杰, 等. 肝門部膽管癌預后因素分析 [J]. 腫瘤, 2005, 25(2): 166169.
5. 張永杰, 俞文隆, 黃立嵩, 等. 聯合肝葉切除及區域淋巴清掃治療肝門部膽管癌的初步觀察 [J]. 外科理論與實踐, 2005, 10(4): 323327.
6. Kondo S, Hirano S, Ambo Y, et al. Forty consecutive resections of hilar cholangiocarcinoma with no postoperative mortality and no positive ductal margins: results of a prospective study [J]. Ann Surg, 2004, 240(1): 95101.
7. Povoski SP, Karpeh MS Jr, Conlon KC, et al. Preoperative biliary drainage: impact on intraoperative bile cultures and infectious morbidity and mortality after pancreaticoduodenectomy [J]. J Gastrointest Surg, 1993, 3(5): 496505.
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. Pisters PW, Hudec WA, Hess KR, et al. Effect of preoperative biliary decompression on pancreaticoduodenectomyassociated morbidity in 300 consecutive patients [J]. Ann Surg, 2001, 234(1): 4755.
10. Martignoni ME, Wagner M, Krhenbühl L, et al. Effect of preoperative biliary drainage on surgical outcome after pancreatoduodenectomy [J]. Am J Surg, 2001, 181(1): 5259.
11. Srivastava S, Sikora SS, Kumar A, et al. Outcome following pancreaticoduodenectomy in patients undergoing preoperative biliary drainage [J]. Dig Surg, 2001, 18(5): 381387.
12. Sewnath ME, Karsten TM, Prins MH, et al. A metaanalysis on the efficacy of preoperative biliary drainage for tumors causing obstructive jaundice [J]. Ann Surg, 2002, 236(1): 1727.
13. Cherqui D, Benoist S, Malassagne B, et al. Major liver resection for carcinoma in jaundiced patients without preoperative biliary drainage [J]. Arch Surg, 2000, 135(3): 302308.
14. Mizuta A, Chijiiwa K, Saiki S, et al. Differences in biliary lipid excretion after major hepatectomy in obstructive jaundiced rats with preoperative internal, external, or no biliary drainage [J]. Eur Surg Res, 2002, 34(4): 291299.
15. Sano T, Ajiki T, Takeyama Y, et al. Internal biliary drainage improves decreased number of gut mucosal T lymphocytes and MAdCAM1 expression in jaundiced rats [J]. Surgery, 2004, 136(3): 693699.
16. Hayata A, Takeuchi E, Nagino M, et al. Hepatocyte growth factor concentration in rat bile is affected by hepatic resection volume and external biliary drainage [J]. J Surg Res, 1999, 85(1): 7176.
17. Ueda J, Chijiiwa K, Nakano K, et al. Lack of intestinal bile results in delayed liver regeneration of normal rat liver after hepatectomy accompanied by impaired cyclin Eassociated kinase activity [J]. Surgery, 2002, 131(5): 564573.
18. Zarnegar R, Michalopoulos GK. The many faces of hepatocyte growth factor: from hepatopoiesis to hematopoiesis [J]. J Cell Biol, 1995, 129(5): 11771180.
19. Fausto N, Campbell JS, Riehle KJ. Liver regeneration [J]. Hepatology, 2006, 43(2 Suppl 1): S4553.
20. Takushi Y, Shiraishi M, Nozato E, et al. Expression of antiapoptotic protein, Bcl2, in liver regeneration after a partial hepatectomy [J]. J Surg Res, 2006, 134(1): 93101.
21. Yamamoto K, Morishita R, Hayashi S, et al. Contribution of Bcl2, but not BclxL and Bax, to antiapoptotic actions of hepatocyte growth factor in hypoxiaconditioned human endothelial cells [J]. Hypertension, 2001, 37(5): 13411348.
22. 韓德五. 肝功能不全//梁擴寰,李紹白. 肝臟病學 [M]. 第2版. 北京: 人民衛生出版社, 2003: 497513.
23. Guerrieri F, Muolo L, Cocco T, et al. Correlation between rat liver regeneration and mitochondrial energy metabolism [J]. Biochim Biophys Acta, 1995, 1272(2): 95100.
24. Hochwald SN, Burke EC, Jarnagin WR, et al. Association of preoperative biliary stenting with increased postoperative infectious complications in proximal cholangiocarcinoma [J]. Arch Surg, 1999, 134(3): 261266.
25. Sakata J, Shirai Y, Wakai T, et al. Catheter tract implantation metastases associated with percutaneous biliary drainage for extrahepatic cholangiocarcinoma [J]. World J Gastroenterol, 2005, 11(44): 70247027.
26. Seyama Y, Kubota K, Sano K, et al. Longterm outcome of extended hemihepatectomy for hilar bile duct Cancer with no mortality and high survival rate [J]. Ann Surg, 2003, 238(1): 7383.

《中國普外基礎與臨床雜志》

肝切除聯合膽腸內引流對梗阻性黃疸大鼠的影響

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《中國普外基礎與臨床雜志》

肝切除聯合膽腸內引流對梗阻性黃疸大鼠的影響

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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