• 浙江大學(xué)醫(yī)學(xué)院附屬第一醫(yī)院肝膽胰外科，衛(wèi)生部多器官聯(lián)合移植重點(diǎn)研究實(shí)驗(yàn)室（杭州 310003）;

目的 介紹小體積肝移植術(shù)后移植物損傷機(jī)理及移植物保護(hù)措施。
方法 復(fù)習(xí)和總結(jié)了相關(guān)文獻(xiàn)資料并作綜述。
結(jié)果 小體積肝移植術(shù)后過高的門靜脈壓力導(dǎo)致移植物機(jī)械性損傷，并通過改變肝竇微循環(huán)狀態(tài)及激活各類細(xì)胞因子使移植物損傷進(jìn)一步加重。通過手術(shù)或藥物的方法降低門靜脈壓力可對移植物起一定的保護(hù)作用。
結(jié)論 了解小體積肝移植術(shù)后移植物損傷機(jī)理對于臨床提高活體肝移植的效果具有積極的意義。

引用本文： 梁靚,梁廷波. 小體積肝移植的基礎(chǔ)研究進(jìn)展. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(5): 428-432. doi: 復(fù)制

1. Bismuth H, Houssin D. Reduced-sized orthotopic liver graft in hepatic transplantation in children [J]. Surgery， 1984; 95(3): 367-370.
2. Strong RW, Lynch SV, Ong TH, et al. Successful liver transplantation from a living donor to her son [J]. N Engl J Med, 1990; 322(21): 1505-1507.
3. Heaton N. Small-for-size liver syndrome after auxiliary and split liver transplantation: donor selection [J]. Liver Transpl, 2003; 9(9): S26-S28.
4. Urata K, Hashikura Y, Ikegami T, et al. Standard liver volume in adults [J]. Transplant Proc, 2000; 32(7): 2093-2094.
5. Kiuchi T, Kasahara M, Uryuhara K, et al. Impact of graft size mismatching on graft prognosis in liver transplantation from living donors[J]. Transplantation, 1999; 67(2): 321-327.
6. Emond JC, Renz JF, Ferrell LD, et al. Functional analysis of grafts from living donors. Implications for the treatment of older recipients [J]. Ann Surg, 1996; 224(4): 544-552.
7. Nishizaki T, Ikegami T, Hiroshige S, et al. Small graft for living donor liver transplantation [J]. Ann Surg, 2001; 233(4): 575-580.
8. Ohkohchi N, Shibuya H, Tsukamoto S, et al. Kupffer’s cells modulate neutrophile activity by superoxide anion and tumor necrosis factor-delta in reperfusion injury of liver transplantation-mechanisms of radical generation and reperfusion injury after cold ischemia [J]. Transplant Proc, 1999; 31(1-2): 1055-1058.
9. Ku Y, Fukumoto T, Nishida T, et al. Evidence that portal vein decompression improves survival of canine quarter orthotopic liver transplantation [J]. Transplantation, 1995; 59(10): 1388-1392.
10. Man K, Lo CM, Ng IO, et al. Liver transplantation in rats using small-for-size grafts: a study of hemodynamic and morphological changes [J]. Arch Surg, 2001; 136(3): 280-285.
11. García-Valdecasas JC, Fuster J, Charco R, et al. Changes in portal vein flow after adult living-donor liver transplantation: does it influence postoperative liver function? [J]. Liver Transpl, 2003; 9(6): 564-569.
12. Troisi R, de Hemptinne B. Clinical relevance of adapting portal vein flow in living donor liver transplantation in adult patients [J]. Liver Transpl, 2003; 9(9): S36-S41.
13. Man K, Fan ST, Lo CM, et al. Graft injury in relation to graft size in right lobe live donor liver transplantation: a study of hepatic sinusoidal injury in correlation with portal hemodynamics and intragraft gene expression [J]. Ann Surg, 2003; 237(2): 256-264.
14. Smyrniotis V, Kostopanagiotou G, Kondi A, et al. Hemodynamic interaction between portal vein and hepatic artery flow in small-for-size split liver transplantation [J]. Transpl Int, 2002; 15(7): 355-360.
15. Palmes D, Minin E, Budny T, et al. The endothelin/nitric oxide balance determines small-for-size liver injury after reduced-size rat liver transplantation [J]. Virchows Arch, 2005; 447(4): 731-741.
16. Li J, Liang L, Ma T, et al. Sinusoidal microcirculatory changes after small-for-size liver transplantation in rats [J]. Transpl Int, 2010 Feb 19. [Epub ahead of print].
17. 徐世國， 鄭樹森， 梁廷波, 等. 大鼠不同體積肝移植早期肺組織內(nèi)誘導(dǎo)性一氧化氮合成酶的表達(dá) [J]. 中華肝膽外科雜志, 2005; 11(1): 273-275.
18. Liang TB, Man K, Kin-Wah Lee T, et al. Distinct intragraft response pattern in relation to graft size in liver transplantation [J]. Transplantation, 2003; 75(5): 673-678.
19. Liang T, Xu S, Yu J, et al. Activation pattern of mitogen-activated protein kinases in early phase of different size liver isografts in rats [J]. Liver Transpl, 2005; 11(12): 1527-1532.
20. Mao L, Qiu YD, Fang S, et al. Liver progenitor cells activated after 30% small-for-size liver transplantation in rats: a preliminary study [J]. Transplant Proc, 2008; 40(5): 1635-1640.
21. Huda KA, Guo L, Haga S, et al. Ex vivo adenoviral gene transfer of constitutively activated STAT3 reduces post-transplant liver injury and promotes regeneration in a 20% rat partial liver transplant model [J]. Transpl Int, 2006; 19(5): 415-423.
22. Debonera F, Wang G, Xie J, et al. Severe preservation injury induces Il-6/STAT3 activation with lack of cell cycle progression after partial liver graft transplantation [J]. Am J Transplant, 2004; 4(12): 1964-1971.
23. Zhong Z, Schwabe RF, Kai Y, et al. Liver regeneration is suppressed in small-for-size liver grafts after transplantation: involvement of c-Jun N-terminal kinase, cyclin D1, and defective energy supply [J]. Transplantation, 2006; 82(2): 241-250.
24. Mabuchi A, Mullaney I, Sheard PW, et al. Role of hepatic stellate cell/hepatocyte interaction and activation of hepatic stellate cells in the early phase of liver regeneration in the rat [J]. J Hepatol, 2004; 40(6): 910-916.
25. Yoshizumi T, Taketomi A, Soejima Y, et al. The beneficial role of simultaneous splenectomy in living donor liver transplantation in patients with small-for-size graft [J]. Transpl Int, 2008; 21(9): 833-842.
26. Ito T, Kiuchi T, Yamamoto H, et al. Changes in portal venous pressure in the early phase after living donor liver transplantation: pathogenesis and clinical implications [J]. Transplantation, 2003; 75(8): 1313-1317.
27. Yagi S, Iida T, Hori T, et al. Optimal portal venous circulation for liver graft function after living-donor liver transplantation [J]. Transplantation, 2006; 81(3): 373-378.
28. Troisi R, de Hemptinne B. Clinical relevance of adapting portal vein flow in living donor liver transplantation in adult patients [J]. Liver Transpl, 2003; 9(9): S36-S41.
29. Reynaert H, Vaeyens F, Qin H, et al. Somatostatin suppresses endothelin-1-induced rat hepatic stellate cell contraction via somatostatin receptor subtype 1 [J]. Gastroenterology, 2001; 121(4): 915-930.
30. Xu X, Man K, Zheng SS, et al. Attenuation of acute phase shear stress by somatostatin improves small-for-size liver graft survival [J]. Liver Transpl, 2006; 12(4): 621-627.
31. Man K, Lee TK, Liang TB, et al. FK 409 ameliorates small-for-size liver graft injury by attenuation of portal hypertension and down-regulation of Egr-1 pathway [J]. Ann Surg, 2004; 240(1): 159-168.
32. Tenhunen R, Marver HS, Schmid R. The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase [J]. Proc Natl Acad Sci USA, 1968; 61(2): 748-755.
33. Yang ZF, Tsui TY, Ho DW, et al. Heme oxygenase-1 potentiates the survival of small-for-size liver graft [J]. Liver Transpl, 2004; 10(6): 784-793.
34. Tang LM, Wang YP, Wang K, et al. Exogenous biliverdin ameliorates ischemia-reperfusion injury in small-for-size rat liver grafts [J]. Transplant Proc, 2007; 39(5): 1338-1344.
35. Morioka D, Kubota T, Sekido H, et al. Prostaglandin E1 improved the function of transplanted fatty liver in a rat reduced-size-liver transplantation model under conditions of permissible cold preservation [J]. Liver Transpl, 2003; 9(1): 79-86.
36. Tang LM, Wang YP, Wang K, et al. Protective effect of adenosine A2A receptor activation in small-for-size liver transplantation [J]. Transpl Int, 2007; 20(1): 93-101.
37. Zhao Y, Man K, Lo CM, et al. Attenuation of small-for-size liver graft injury by FTY720: significance of cell-survival Akt signaling pathway [J]. Am J Transplant, 2004; 4(9): 1399-1407.
38. Yu Y, Yao AH, Chen N, et al. Mesenchymal stem cells over-expressing hepatocyte growth factor improve small-for-size liver grafts regeneration [J]. Mol Ther, 2007; 15(7): 1382-1389.
39. Song J, Zhang YW, Yao AH, et al. Adenoviral cardiotrophin-1 transfer improves survival and early graft function after ischemia and reperfusion in rat small-for-size liver transplantation model [J]. Transpl Int, 2008; 21(4): 372-383.
40. Ricciardi R, Schaffer BK, Shah SA, et al. Bosentan, an endothelin antagonist, augments hepatic graft function by reducing graft circulatory impairment following ischemia/reperfusion injury [J]. J Gastrointest Surg, 2001; 5(3): 322-329.
41. Palmes D, Budny TB, Stratmann U, et al. Endothelin-A receptor antagonist reduces microcirculatory disturbances and transplant dysfunction after partial liver transplantation [J]. Liver Transpl, 2003; 9(9): 929-939.
42. Liang L, Ma T, Chen W, et al. Therapeutic potential and related signal pathway of adipose-derived stem cell transplantation for rat liver injury [J]. Hepatol Res, 2009; 39(8): 822-832.
  1. 1. Bismuth H, Houssin D. Reduced-sized orthotopic liver graft in hepatic transplantation in children [J]. Surgery， 1984; 95(3): 367-370.
  2. 2. Strong RW, Lynch SV, Ong TH, et al. Successful liver transplantation from a living donor to her son [J]. N Engl J Med, 1990; 322(21): 1505-1507.
  3. 3. Heaton N. Small-for-size liver syndrome after auxiliary and split liver transplantation: donor selection [J]. Liver Transpl, 2003; 9(9): S26-S28.
  4. 4. Urata K, Hashikura Y, Ikegami T, et al. Standard liver volume in adults [J]. Transplant Proc, 2000; 32(7): 2093-2094.
  5. 5. Kiuchi T, Kasahara M, Uryuhara K, et al. Impact of graft size mismatching on graft prognosis in liver transplantation from living donors[J]. Transplantation, 1999; 67(2): 321-327.
  6. 6. Emond JC, Renz JF, Ferrell LD, et al. Functional analysis of grafts from living donors. Implications for the treatment of older recipients [J]. Ann Surg, 1996; 224(4): 544-552.
  7. 7. Nishizaki T, Ikegami T, Hiroshige S, et al. Small graft for living donor liver transplantation [J]. Ann Surg, 2001; 233(4): 575-580.
  8. 8. Ohkohchi N, Shibuya H, Tsukamoto S, et al. Kupffer’s cells modulate neutrophile activity by superoxide anion and tumor necrosis factor-delta in reperfusion injury of liver transplantation-mechanisms of radical generation and reperfusion injury after cold ischemia [J]. Transplant Proc, 1999; 31(1-2): 1055-1058.
  9. 9. Ku Y, Fukumoto T, Nishida T, et al. Evidence that portal vein decompression improves survival of canine quarter orthotopic liver transplantation [J]. Transplantation, 1995; 59(10): 1388-1392.
  10. 10. Man K, Lo CM, Ng IO, et al. Liver transplantation in rats using small-for-size grafts: a study of hemodynamic and morphological changes [J]. Arch Surg, 2001; 136(3): 280-285.
  11. 11. García-Valdecasas JC, Fuster J, Charco R, et al. Changes in portal vein flow after adult living-donor liver transplantation: does it influence postoperative liver function? [J]. Liver Transpl, 2003; 9(6): 564-569.
  12. 12. Troisi R, de Hemptinne B. Clinical relevance of adapting portal vein flow in living donor liver transplantation in adult patients [J]. Liver Transpl, 2003; 9(9): S36-S41.
  13. 13. Man K, Fan ST, Lo CM, et al. Graft injury in relation to graft size in right lobe live donor liver transplantation: a study of hepatic sinusoidal injury in correlation with portal hemodynamics and intragraft gene expression [J]. Ann Surg, 2003; 237(2): 256-264.
  14. 14. Smyrniotis V, Kostopanagiotou G, Kondi A, et al. Hemodynamic interaction between portal vein and hepatic artery flow in small-for-size split liver transplantation [J]. Transpl Int, 2002; 15(7): 355-360.
  15. 15. Palmes D, Minin E, Budny T, et al. The endothelin/nitric oxide balance determines small-for-size liver injury after reduced-size rat liver transplantation [J]. Virchows Arch, 2005; 447(4): 731-741.
  16. 16. Li J, Liang L, Ma T, et al. Sinusoidal microcirculatory changes after small-for-size liver transplantation in rats [J]. Transpl Int, 2010 Feb 19. [Epub ahead of print].
  17. 17. 徐世國， 鄭樹森， 梁廷波, 等. 大鼠不同體積肝移植早期肺組織內(nèi)誘導(dǎo)性一氧化氮合成酶的表達(dá) [J]. 中華肝膽外科雜志, 2005; 11(1): 273-275.
  18. 18. Liang TB, Man K, Kin-Wah Lee T, et al. Distinct intragraft response pattern in relation to graft size in liver transplantation [J]. Transplantation, 2003; 75(5): 673-678.
  19. 19. Liang T, Xu S, Yu J, et al. Activation pattern of mitogen-activated protein kinases in early phase of different size liver isografts in rats [J]. Liver Transpl, 2005; 11(12): 1527-1532.
  20. 20. Mao L, Qiu YD, Fang S, et al. Liver progenitor cells activated after 30% small-for-size liver transplantation in rats: a preliminary study [J]. Transplant Proc, 2008; 40(5): 1635-1640.
  21. 21. Huda KA, Guo L, Haga S, et al. Ex vivo adenoviral gene transfer of constitutively activated STAT3 reduces post-transplant liver injury and promotes regeneration in a 20% rat partial liver transplant model [J]. Transpl Int, 2006; 19(5): 415-423.
  22. 22. Debonera F, Wang G, Xie J, et al. Severe preservation injury induces Il-6/STAT3 activation with lack of cell cycle progression after partial liver graft transplantation [J]. Am J Transplant, 2004; 4(12): 1964-1971.
  23. 23. Zhong Z, Schwabe RF, Kai Y, et al. Liver regeneration is suppressed in small-for-size liver grafts after transplantation: involvement of c-Jun N-terminal kinase, cyclin D1, and defective energy supply [J]. Transplantation, 2006; 82(2): 241-250.
  24. 24. Mabuchi A, Mullaney I, Sheard PW, et al. Role of hepatic stellate cell/hepatocyte interaction and activation of hepatic stellate cells in the early phase of liver regeneration in the rat [J]. J Hepatol, 2004; 40(6): 910-916.
  25. 25. Yoshizumi T, Taketomi A, Soejima Y, et al. The beneficial role of simultaneous splenectomy in living donor liver transplantation in patients with small-for-size graft [J]. Transpl Int, 2008; 21(9): 833-842.
  26. 26. Ito T, Kiuchi T, Yamamoto H, et al. Changes in portal venous pressure in the early phase after living donor liver transplantation: pathogenesis and clinical implications [J]. Transplantation, 2003; 75(8): 1313-1317.
  27. 27. Yagi S, Iida T, Hori T, et al. Optimal portal venous circulation for liver graft function after living-donor liver transplantation [J]. Transplantation, 2006; 81(3): 373-378.
  28. 28. Troisi R, de Hemptinne B. Clinical relevance of adapting portal vein flow in living donor liver transplantation in adult patients [J]. Liver Transpl, 2003; 9(9): S36-S41.
  29. 29. Reynaert H, Vaeyens F, Qin H, et al. Somatostatin suppresses endothelin-1-induced rat hepatic stellate cell contraction via somatostatin receptor subtype 1 [J]. Gastroenterology, 2001; 121(4): 915-930.
  30. 30. Xu X, Man K, Zheng SS, et al. Attenuation of acute phase shear stress by somatostatin improves small-for-size liver graft survival [J]. Liver Transpl, 2006; 12(4): 621-627.
  31. 31. Man K, Lee TK, Liang TB, et al. FK 409 ameliorates small-for-size liver graft injury by attenuation of portal hypertension and down-regulation of Egr-1 pathway [J]. Ann Surg, 2004; 240(1): 159-168.
  32. 32. Tenhunen R, Marver HS, Schmid R. The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase [J]. Proc Natl Acad Sci USA, 1968; 61(2): 748-755.
  33. 33. Yang ZF, Tsui TY, Ho DW, et al. Heme oxygenase-1 potentiates the survival of small-for-size liver graft [J]. Liver Transpl, 2004; 10(6): 784-793.
  34. 34. Tang LM, Wang YP, Wang K, et al. Exogenous biliverdin ameliorates ischemia-reperfusion injury in small-for-size rat liver grafts [J]. Transplant Proc, 2007; 39(5): 1338-1344.
  35. 35. Morioka D, Kubota T, Sekido H, et al. Prostaglandin E1 improved the function of transplanted fatty liver in a rat reduced-size-liver transplantation model under conditions of permissible cold preservation [J]. Liver Transpl, 2003; 9(1): 79-86.
  36. 36. Tang LM, Wang YP, Wang K, et al. Protective effect of adenosine A2A receptor activation in small-for-size liver transplantation [J]. Transpl Int, 2007; 20(1): 93-101.
  37. 37. Zhao Y, Man K, Lo CM, et al. Attenuation of small-for-size liver graft injury by FTY720: significance of cell-survival Akt signaling pathway [J]. Am J Transplant, 2004; 4(9): 1399-1407.
  38. 38. Yu Y, Yao AH, Chen N, et al. Mesenchymal stem cells over-expressing hepatocyte growth factor improve small-for-size liver grafts regeneration [J]. Mol Ther, 2007; 15(7): 1382-1389.
  39. 39. Song J, Zhang YW, Yao AH, et al. Adenoviral cardiotrophin-1 transfer improves survival and early graft function after ischemia and reperfusion in rat small-for-size liver transplantation model [J]. Transpl Int, 2008; 21(4): 372-383.
  40. 40. Ricciardi R, Schaffer BK, Shah SA, et al. Bosentan, an endothelin antagonist, augments hepatic graft function by reducing graft circulatory impairment following ischemia/reperfusion injury [J]. J Gastrointest Surg, 2001; 5(3): 322-329.
  41. 41. Palmes D, Budny TB, Stratmann U, et al. Endothelin-A receptor antagonist reduces microcirculatory disturbances and transplant dysfunction after partial liver transplantation [J]. Liver Transpl, 2003; 9(9): 929-939.
  42. 42. Liang L, Ma T, Chen W, et al. Therapeutic potential and related signal pathway of adipose-derived stem cell transplantation for rat liver injury [J]. Hepatol Res, 2009; 39(8): 822-832.