• 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  探討骨髓間充質(zhì)干細(xì)胞(BMSCs)移植修復(fù)大鼠肝缺血再灌注損傷的最佳劑量,為細(xì)胞移植修復(fù)肝缺血再灌注損傷提供前期的實(shí)驗(yàn)依據(jù)。
方法  采用全骨髓直接貼壁法分離培養(yǎng)BMSCs,取第4代細(xì)胞進(jìn)行移植。將30只健康雄性Wistar大鼠建立肝缺血再灌注損傷模型后,隨機(jī)分成空白對(duì)照組、5×105個(gè)組、1×106個(gè)組、2×106個(gè)組及3×106個(gè)組5組,每組6只。后4組大鼠均在建立肝缺血再灌注損傷模型后,立即抽取200 μL細(xì)胞懸液(數(shù)量分別為5×105、1×106、2×106及3×106個(gè)),通過(guò)門靜脈注射;空白對(duì)照組大鼠注射等體積的PBS溶液。于移植術(shù)后24 h采血檢測(cè)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;取肝臟組織檢測(cè)丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性及核因子-κB (NF-κB) p65蛋白的表達(dá),并行HE染色。
結(jié)果  1×106個(gè)組和2×106個(gè)組與空白對(duì)照組、5×105個(gè)組及3×106個(gè)組比較,其AST、ALT及MDA水平均降低(P<
0.05),而SOD活性均增高(P<0.05);NF-κB p65蛋白的表達(dá)均明顯下調(diào);肝組織的病理學(xué)損傷均改善。但該2組的AST、ALT、MDA及SOD水平比較差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05),且肝組織的病理學(xué)改變也無(wú)明顯差別。
結(jié)論  大鼠BMSCs移植治療肝缺血再灌注損傷的最佳劑量為1×106個(gè)細(xì)胞。

引用本文: 喬鵬飛,金光鑫,吳德全. 骨髓間充質(zhì)干細(xì)胞移植修復(fù)大鼠肝缺血再灌注損傷最佳劑量的研究. 中國(guó)普外基礎(chǔ)與臨床雜志, 2013, 20(9): 1018-1022. doi: 復(fù)制

版權(quán)信息: ?四川大學(xué)華西醫(yī)院華西期刊社《中國(guó)普外基礎(chǔ)與臨床雜志》版權(quán)所有,未經(jīng)授權(quán)不得轉(zhuǎn)載、改編

1. Fan C, Zwacka RM, Engelhardt JF. Therapeutic approaches for ischemia/reperfusion injury in the liver[J]. J Mol Med (Berl), 1999, 77(8):577-592.
2. Kanazawa H, Fujimoto Y, Teratani T, et al. Bone marrow-derivedmesenchymal stem cells ameliorate hepatic ischemia reperfusion injury in a rat model[J]. PLoS One, 2011, 6(4):e19195.
3. 金光鑫, 喬鵬飛, 胡彥華, 等. 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[J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2013, 20(1):60-65.
4. 石臣磊, 秦華東, 丁超. 依達(dá)拉奉對(duì)肝缺血再灌注損傷逆轉(zhuǎn)作用的研究[J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2011, 18(8):887-889.
5. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells[J]. Science, 1999, 284(5411):143-147.
6. Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement[J]. Cytotherapy,.
7. Casiraghi F, Azzollini N, Cassis P, et al. Pretransplant infusion of mesenchymal stem cells prolongs the survival of a semiallogeneic heart transplant through the generation of regulatory T cells[J]. J Immunol, 2008, 181(6):3933-3946.
8. Chabannes D, Hill M, Merieau E, et al. A role for heme oxyge-nase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells[J]. Blood, 2007, 110(10):3691-3694.
9. Popp FC, Eggenhofer E, Renner P, et al. Mesenchymal stem cells can induce long-term acceptance of solid organ allografts in synergy with low-dose mycophenolate[J]. Transpl Immunol, 2008, 20(1-2):55-60.
10. Sbano P, Cuccia A, Mazzanti B, et al. Use of donor bone marrowmesenchymal stem cells for treatment of skin allograft rejection in a preclinical rat model[J]. Arch Dermatol Res, 2008, 300(3):115-124.
11. Zwacka RM, Zhang Y, Halldorson J, et al. CD4+ T-lympho-cytes mediate ischemia/reperfusion-induced inflammatory responsesin mouse liver[J]. J Clin Invest, 1997, 100(2):279-289.
12. Jaeschke H, Bautista AP, Spolarics Z, et al. Superoxide generation by Kupffer cells and priming of neutrophils during reperfusion after hepatic ischemia[J]. Free Radic Res Commun, 1991, 15(5):.
13. Hernandez LA, Grisham MB, Twohig B, et al. Role of neutrophils in ischemia-reperfusion-induced microvascular injury[J]. Am J Physiol, 1987, 253 (3 Pt 2):H699-H703.
14. Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regene-rate infarcted myocardium[J]. Nature, 2001, 410(6829):701-705.
15. 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.
16. Sen R, Baltimore D. Multiple nuclear factors interact with theimmunoglobulin enhancer sequences[J]. Cell, 1986, 46(5):705-716.
17. León Fernández OS, Ajamieh HH, Berlanga J, et al. Ozone oxid-ative preconditioning is mediated by A1 adenosine receptors in a rat model of liver ischemia/reperfusion[J]. Transpl Int, 2008, 21(1):39-48.
18. -284.
19. , 8(4):315-317.
  1. 1. Fan C, Zwacka RM, Engelhardt JF. Therapeutic approaches for ischemia/reperfusion injury in the liver[J]. J Mol Med (Berl), 1999, 77(8):577-592.
  2. 2. Kanazawa H, Fujimoto Y, Teratani T, et al. Bone marrow-derivedmesenchymal stem cells ameliorate hepatic ischemia reperfusion injury in a rat model[J]. PLoS One, 2011, 6(4):e19195.
  3. 3. 金光鑫, 喬鵬飛, 胡彥華, 等. 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[J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2013, 20(1):60-65.
  4. 4. 石臣磊, 秦華東, 丁超. 依達(dá)拉奉對(duì)肝缺血再灌注損傷逆轉(zhuǎn)作用的研究[J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2011, 18(8):887-889.
  5. 5. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells[J]. Science, 1999, 284(5411):143-147.
  6. 6. Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement[J]. Cytotherapy,.
  7. 7. Casiraghi F, Azzollini N, Cassis P, et al. Pretransplant infusion of mesenchymal stem cells prolongs the survival of a semiallogeneic heart transplant through the generation of regulatory T cells[J]. J Immunol, 2008, 181(6):3933-3946.
  8. 8. Chabannes D, Hill M, Merieau E, et al. A role for heme oxyge-nase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells[J]. Blood, 2007, 110(10):3691-3694.
  9. 9. Popp FC, Eggenhofer E, Renner P, et al. Mesenchymal stem cells can induce long-term acceptance of solid organ allografts in synergy with low-dose mycophenolate[J]. Transpl Immunol, 2008, 20(1-2):55-60.
  10. 10. Sbano P, Cuccia A, Mazzanti B, et al. Use of donor bone marrowmesenchymal stem cells for treatment of skin allograft rejection in a preclinical rat model[J]. Arch Dermatol Res, 2008, 300(3):115-124.
  11. 11. Zwacka RM, Zhang Y, Halldorson J, et al. CD4+ T-lympho-cytes mediate ischemia/reperfusion-induced inflammatory responsesin mouse liver[J]. J Clin Invest, 1997, 100(2):279-289.
  12. 12. Jaeschke H, Bautista AP, Spolarics Z, et al. Superoxide generation by Kupffer cells and priming of neutrophils during reperfusion after hepatic ischemia[J]. Free Radic Res Commun, 1991, 15(5):.
  13. 13. Hernandez LA, Grisham MB, Twohig B, et al. Role of neutrophils in ischemia-reperfusion-induced microvascular injury[J]. Am J Physiol, 1987, 253 (3 Pt 2):H699-H703.
  14. 14. Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regene-rate infarcted myocardium[J]. Nature, 2001, 410(6829):701-705.
  15. 15. 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.
  16. 16. Sen R, Baltimore D. Multiple nuclear factors interact with theimmunoglobulin enhancer sequences[J]. Cell, 1986, 46(5):705-716.
  17. 17. León Fernández OS, Ajamieh HH, Berlanga J, et al. Ozone oxid-ative preconditioning is mediated by A1 adenosine receptors in a rat model of liver ischemia/reperfusion[J]. Transpl Int, 2008, 21(1):39-48.
  18. 18. -284.
  19. 19. , 8(4):315-317.
  • 下一篇

    納米碳甲狀旁腺負(fù)顯影辨認(rèn)保護(hù)技術(shù)在甲狀腺癌手術(shù)中的應(yīng)用△