• 1.哈爾濱醫(yī)科大學(xué)附屬第一醫(yī)院急診外科(黑龍江哈爾濱 150001);;
  • 2.哈爾濱醫(yī)科大學(xué)附屬第二醫(yī)院普外科(黑龍江哈爾濱 150086);

目的  探討同種異體骨髓間充質(zhì)干細(xì)胞(BM-MSCs)對大鼠肝臟熱缺血再灌注損傷的保護(hù)作用。
方法  取10只健康Wistar大鼠骨髓,體外分離、培養(yǎng)間充質(zhì)干細(xì)胞,對其進(jìn)行生物學(xué)鑒定,并對門靜脈途徑移植入肝臟的間充質(zhì)干細(xì)胞行4,6-聯(lián)脒-2-苯基吲哚(DAPI)染色示蹤。建立大鼠70%肝臟缺血再灌注損傷模型,將32只雄性Wistar大鼠隨機(jī)分成假手術(shù)組(Sham組)、缺血再灌注組(I/R組)、維生素C治療組(VC組)及BM-MSCs組,每組8只,分別于再灌注24h后取材,檢測血清天門冬氨酸氨基轉(zhuǎn)移酶(AST)和丙氨酸氨基轉(zhuǎn)移酶(ALT)水平,肝臟組織總超氧化物歧化酶(SOD)和丙二醛(MDA)含量,并對肝臟組織行HE染色觀察病理學(xué)改變,TUNEL法檢測肝臟凋亡指數(shù)(AI)。
結(jié)果  體外分離的BM-MSCs生長穩(wěn)定,增殖旺盛,表達(dá)CD29及CD44,不表達(dá)CD34及CD45; 大鼠肝臟缺血再灌注損傷模型穩(wěn)定,在肝臟組織切片內(nèi)見間充質(zhì)干細(xì)胞定植,多位于肝小葉中央靜脈周圍。VC組和BM-MSCs組的AST、ALT、MDA和AI均較I/R組低(P<0.05),SOD均較I/R組高(P<0.05); BM-MSCs組的AST、ALT、MDA和AI均低于VC組(P<0.05),SOD高于VC組(P<0.05)。
結(jié)論  BM-MSCs可通過減輕氧化應(yīng)激損傷和抑制肝細(xì)胞凋亡,來保護(hù)大鼠肝臟熱缺血再灌注損傷。

引用本文: 金光鑫,喬鵬飛,胡彥華,仇公才,高峰,吳德全. 同種異體骨髓間充質(zhì)干細(xì)胞保護(hù)大鼠肝臟熱缺血再灌注損傷的研究. 中國普外基礎(chǔ)與臨床雜志, 2013, 20(1): 60-65. doi: 復(fù)制

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1. Glantzounis GK, Salacinski HJ, Yang W, et al. The contemporary role of antioxidant therapy in attenuating liver ischemia-reperfusion injury:a review[J]. Liver Transpl, 2005, 11(9):1031-1047.
2. Coriat R, Leconte M, Kavian N,et al. Mangafodipir protects against hepatic ischemia-reperfusion injury in mice[J]. PLoS ONE, 2011, 6(11):e27005.
3. Loffredo FS, Steinhauser ML, Gannon J, et al. Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair[J]. Cell Stem Cell, 2011, 8(4):389-398.
4. Gatti S, Bruno S, Deregibus MC, et al. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury[J]. NephrolDial Transplant, 2011, 26(5):1474-1483.
5. Liu L, Cao JX, Sun B, et al. Mesenchymal stem cells inhibition of chronic ethanol-induced oxidative damage via upregulation of phosphatidylinositol-3-kinase/Akt and modulation of extracellular signal-regulated kinase 1/2 activation in PC12 cells and neurons[J]. Neuroscience, 2010, 167(4):1115-1124.
6. 高峰, 李國良, 林雨佳, 等. 骨髓間充質(zhì)干細(xì)胞移植途徑對胰島移植物免疫排斥反應(yīng)的影響[J]. 中國普通外科雜志, 2012, 21(9):1080-1085.
7. 石臣磊, 秦華東, 丁超. 依達(dá)拉奉對肝缺血再灌注損傷逆轉(zhuǎn)作用的研究[J]. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(8):887-889.
8. Hu YH, Wu DQ, Gao F, et al. A secretory function of human insulin-producing cells in vivo[J]. Hepatobiliary Pancreat Dis Int, 2009, 8(3):255-260.
9. Hassan-Khabbar S, Vamy M, Cottart CH, et al. Protective effectof post-ischemic treatment with trans-resveratrol on cytokineproduction and neutrophil recruitment by rat liver[J]. Biochimie,2010, 92(4):405-410.
10. Jaeschke H. Reactive oxygen and ischemia/reperfusion injury of the liver[J]. Chem Biol Interact, 1991, 79(2):115-136.
11. McCord JM. Oxygen-derived free radicals in postischemic tissue injury[J]. N Engl J Med, 1985, 312(3):159-163.
12. Georgiev P, Dahm F, Graf R, et al. Blocking the path to death:anti-apoptotic molecules in ischemia/reperfusion injury of the liver[J]. Curr Pharm Des, 2006, 12(23):2911-2921.
13. Jaeschke H, Lemasters JJ. Apoptosis versus oncotic necrosis in hepatic ischemia/reperfusion injury[J]. Gastroenterology, 2003, 125(4):1246-1257.
14. Sasaki H, Matsuno T, Nakagawa K, et al. Superoxide induces hepatocyte apoptosis during the early phase of reperfusion after murine liver ischemia[J]. Transplant Proc, 1998, 30(7):2958-2959.
15. Seo MY, Lee SM. Protective effect of low dose of ascorbic acid on hepatobiliary function in hepatic ischemia/reperfusion in rats[J]. J Hepatol, 2002, 36(1):72-77.
16. 霍鑫, 馮金煒, 劉方峰, 等. pEGFP-C1/Akt體外轉(zhuǎn)染骨髓間充質(zhì)干細(xì)胞對后肢缺血大鼠血管生成的影響[J]. 中國普外基礎(chǔ)與臨床雜志, 2008, 15(6):402-407.
17. 吳德全, 胡彥華, 高峰, 等. 凍存對人臍血間充質(zhì)干細(xì)胞生物學(xué)特性的影響[J]. 中國普外基礎(chǔ)與臨床雜志, 2008(1):36-40.
18. Pan RL, Wang P, Xiang LX, et al. Delta-like 1 serves as a new target and contributor to liver fibrosis down-regulated by mesenchymal stem cell transplantation[J]. J Biol Chem, 2011, 286(14):12340-12348.
19. Angoulvant D, Ivanes F, Ferrera R, et al. Mesenchymal stem cell conditioned media attenuates in vitro and ex vivo myocardial reperfusion injury[J]. J Heart Lung Transplant, 2011, 30(1):95-102.
20. Kuo TK, Hung SP, Chuang CH, et al. Stem cell therapy for liver disease:parameters governing the success of using bone marrow mesenchymal stem cells[J]. Gastroenterology, 2008, 134(7):2111-2121.
21. Banas A, Teratani T, Yamamoto Y, et al. IFATS collection:in vivo therapeutic potential of human adipose tissue mesenchymal stem cells after transplantation into mice with liver injury[J]. Stem Cells, 2008, 26(10):2705-2712.
22. Parekkadan B, van Poll D, Suganuma K, et al. Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure[J]. PLoS One, 2007, 2(9):e941.
23. Tsai PC, Fu TW, Chen YM, et al. The therapeutic potential of human umbilical mesenchymal stem cells from Wharton’s jelly in the treatment of rat liver fibrosis[J]. Liver Transpl, 2009, 15(5):484-495.
24. Chang YJ, Liu JW, Lin PC, et al. Mesenchymal stem cells facilitate recovery from chemically induced liver damage and decrease liver fibrosis[J]. Life Sci, 2009, 85(13-14):517-525.
25. Dahlke MH, Hoogduijn M, Eggenhofer E, et al. Toward MSC in solid organ transplantation:2008 position paper of the MISOT study group[J]. Transplantation, 2009, 88(5):614-619.
  1. 1. Glantzounis GK, Salacinski HJ, Yang W, et al. The contemporary role of antioxidant therapy in attenuating liver ischemia-reperfusion injury:a review[J]. Liver Transpl, 2005, 11(9):1031-1047.
  2. 2. Coriat R, Leconte M, Kavian N,et al. Mangafodipir protects against hepatic ischemia-reperfusion injury in mice[J]. PLoS ONE, 2011, 6(11):e27005.
  3. 3. Loffredo FS, Steinhauser ML, Gannon J, et al. Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair[J]. Cell Stem Cell, 2011, 8(4):389-398.
  4. 4. Gatti S, Bruno S, Deregibus MC, et al. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury[J]. NephrolDial Transplant, 2011, 26(5):1474-1483.
  5. 5. Liu L, Cao JX, Sun B, et al. Mesenchymal stem cells inhibition of chronic ethanol-induced oxidative damage via upregulation of phosphatidylinositol-3-kinase/Akt and modulation of extracellular signal-regulated kinase 1/2 activation in PC12 cells and neurons[J]. Neuroscience, 2010, 167(4):1115-1124.
  6. 6. 高峰, 李國良, 林雨佳, 等. 骨髓間充質(zhì)干細(xì)胞移植途徑對胰島移植物免疫排斥反應(yīng)的影響[J]. 中國普通外科雜志, 2012, 21(9):1080-1085.
  7. 7. 石臣磊, 秦華東, 丁超. 依達(dá)拉奉對肝缺血再灌注損傷逆轉(zhuǎn)作用的研究[J]. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(8):887-889.
  8. 8. Hu YH, Wu DQ, Gao F, et al. A secretory function of human insulin-producing cells in vivo[J]. Hepatobiliary Pancreat Dis Int, 2009, 8(3):255-260.
  9. 9. Hassan-Khabbar S, Vamy M, Cottart CH, et al. Protective effectof post-ischemic treatment with trans-resveratrol on cytokineproduction and neutrophil recruitment by rat liver[J]. Biochimie,2010, 92(4):405-410.
  10. 10. Jaeschke H. Reactive oxygen and ischemia/reperfusion injury of the liver[J]. Chem Biol Interact, 1991, 79(2):115-136.
  11. 11. McCord JM. Oxygen-derived free radicals in postischemic tissue injury[J]. N Engl J Med, 1985, 312(3):159-163.
  12. 12. Georgiev P, Dahm F, Graf R, et al. Blocking the path to death:anti-apoptotic molecules in ischemia/reperfusion injury of the liver[J]. Curr Pharm Des, 2006, 12(23):2911-2921.
  13. 13. Jaeschke H, Lemasters JJ. Apoptosis versus oncotic necrosis in hepatic ischemia/reperfusion injury[J]. Gastroenterology, 2003, 125(4):1246-1257.
  14. 14. Sasaki H, Matsuno T, Nakagawa K, et al. Superoxide induces hepatocyte apoptosis during the early phase of reperfusion after murine liver ischemia[J]. Transplant Proc, 1998, 30(7):2958-2959.
  15. 15. Seo MY, Lee SM. Protective effect of low dose of ascorbic acid on hepatobiliary function in hepatic ischemia/reperfusion in rats[J]. J Hepatol, 2002, 36(1):72-77.
  16. 16. 霍鑫, 馮金煒, 劉方峰, 等. pEGFP-C1/Akt體外轉(zhuǎn)染骨髓間充質(zhì)干細(xì)胞對后肢缺血大鼠血管生成的影響[J]. 中國普外基礎(chǔ)與臨床雜志, 2008, 15(6):402-407.
  17. 17. 吳德全, 胡彥華, 高峰, 等. 凍存對人臍血間充質(zhì)干細(xì)胞生物學(xué)特性的影響[J]. 中國普外基礎(chǔ)與臨床雜志, 2008(1):36-40.
  18. 18. Pan RL, Wang P, Xiang LX, et al. Delta-like 1 serves as a new target and contributor to liver fibrosis down-regulated by mesenchymal stem cell transplantation[J]. J Biol Chem, 2011, 286(14):12340-12348.
  19. 19. Angoulvant D, Ivanes F, Ferrera R, et al. Mesenchymal stem cell conditioned media attenuates in vitro and ex vivo myocardial reperfusion injury[J]. J Heart Lung Transplant, 2011, 30(1):95-102.
  20. 20. Kuo TK, Hung SP, Chuang CH, et al. Stem cell therapy for liver disease:parameters governing the success of using bone marrow mesenchymal stem cells[J]. Gastroenterology, 2008, 134(7):2111-2121.
  21. 21. Banas A, Teratani T, Yamamoto Y, et al. IFATS collection:in vivo therapeutic potential of human adipose tissue mesenchymal stem cells after transplantation into mice with liver injury[J]. Stem Cells, 2008, 26(10):2705-2712.
  22. 22. Parekkadan B, van Poll D, Suganuma K, et al. Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure[J]. PLoS One, 2007, 2(9):e941.
  23. 23. Tsai PC, Fu TW, Chen YM, et al. The therapeutic potential of human umbilical mesenchymal stem cells from Wharton’s jelly in the treatment of rat liver fibrosis[J]. Liver Transpl, 2009, 15(5):484-495.
  24. 24. Chang YJ, Liu JW, Lin PC, et al. Mesenchymal stem cells facilitate recovery from chemically induced liver damage and decrease liver fibrosis[J]. Life Sci, 2009, 85(13-14):517-525.
  25. 25. Dahlke MH, Hoogduijn M, Eggenhofer E, et al. Toward MSC in solid organ transplantation:2008 position paper of the MISOT study group[J]. Transplantation, 2009, 88(5):614-619.