• 昆明醫(yī)學(xué)院第二附屬醫(yī)院肝膽胰外科(昆明650101);

目的對他克莫司(tacrolimus,F(xiàn)K506)和環(huán)孢素A (cyclosporine A,CsA )在藥代動力學(xué)、藥物作用機理、藥物副作用、臨床應(yīng)用以及與霉酚酸酯(MMF)聯(lián)合用藥的療效等進(jìn)行比較。方法復(fù)習(xí)近年來國內(nèi)外相關(guān)文獻(xiàn)并進(jìn)行分析比較。 結(jié)果FK506在預(yù)防及治療急性排斥反應(yīng),延緩慢性排斥反應(yīng),降低激素用量及移植后心血管病危險等方面較 CsA 有一定的優(yōu)越性,但CsA較FK506術(shù)后糖尿病發(fā)生率低且更為經(jīng)濟。另一方面,F(xiàn)K506或CsA與MMF聯(lián)合應(yīng)用會取得良好療效。結(jié)論FK506及CsA均為安全、有效的免疫抑制劑,術(shù)后可長期服用。

引用本文: 魏曉平,綜述,李立,審校. 他克莫司與環(huán)孢素A在器官移植中的應(yīng)用比較. 中國普外基礎(chǔ)與臨床雜志, 2003, 10(4): 415-418. 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. 陳實主編. 移植免疫學(xué) [M]. 第1版.武漢: 湖北科學(xué)技術(shù)出版社, 1998∶250~259.
2. Hutchinson IV, Bagnall W, Bryce P, et al.Differences in the mode of action of cyclosporine and FK506 [J]. Transplant Proc, 1998; 30(4)∶959.
3. Migita K, Origuchi T,Kawabe Y,et al.FK506 markedly enhances apoptosis of antigenstimulated peripheral T cells by downregulation of BclxL [J]. Transplantation, 1999; 68(7)∶1018.
4. Appleman LJ, Berezovskaya A, Grass I, et al.CD28 costimulation mediates T cell expansion via IL2independent and IL2dependent regulation of cell cycle progression [J]. J Immunol, 2000; 164(1)∶144.
5. Khanna AK,Hosenpud JD.Cyclosporine induces the expression of the cyclin inhibitor p21 [J]. Transplantation,1999; 67(9)∶1262.
6. Datto MB, Yu Y, Wang XF. Functional analysis of the transforming growth factor β responsive elements in the WAF1/Cipl/p21 promoter [J]. J Biol Chem, 1995; 270(48)∶28623.
7. Lee JI, Ganster RW, Geller DA, et al.Cyclosporine A inhibits the expression of costimulatory molecules on in vitrogenerated dendritic cells: association with reduced nuclear translocation of nuclear factor kappa B [J]. Transplantation, 1999; 68(9)∶1255.
8. Neuhaus P,Blumhardt G,Bechstein WO,et al.Comparison of FK506 and cyclosporinebased immunosuppression in primary orthotopic liver transplantation [J]. Transplantation, 1995; 59(1)∶31.
9. Wiesner RH.A longterm comparison of tacrolimus(FK506) versus cyclosporine in liver transplantation: a report of the United States FK506 Study Group [J]. Transplantation, 1998; 66(4)∶493.
10. 季曙明,殷立平,尹廣,等.他克莫司延緩移植腎功能衰竭進(jìn)程的臨床研究 [J]. 中華器官移植雜志, 2000; 21(5)∶291.
11. Wang T,Donahoe PK,Zervos AS.Specific interaction of typeⅠreceptors of the TGFβ family with the immunophilin FKBP12 [J]. Science, 1994; 265(5172)∶674.
12. Mohamed MA, Robertson H, Booth TA, et al. TGFβ expression in renal transplant biopsies:a comparative study between cyclosporinA and tacrolimus [J]. Transplantation, 2000; 69(5)∶1002.
13. Jain A, Mazariegos G, Kashyap R, et al. Comparative longterm evaluation of tacrolimus and cyclosporine in pediatric liver transplantation [J]. Transplantation, 2000; 70(4)∶617.
14. Greig PD.Early steroid withdrawal following liver transplantationtwoyear followup [C]. First Joint Annual Meeting of the American Society of Transplant Surgeons and the American Society of Transplantation.Chicago USA, 2000∶Abstract 1065.
15. Opelz G, Wujciak T, Ritz E.Association of chronic kidney graft failure with recipient blood pressure. [J]. Kidney Int, 1998; 53(1)∶217.
16. Stegall MD, Wachs ME, Everson G, et al.Prednisone withdrawal 14 days after liver transplantation with mycophenolate: a prospective trial of cyclosporine and tacrolimus [J]. Transplantation,1997; 64(12)∶1755.
17. Pirsch JD.Tacrolimus versus cyclosporine in kidney transplantation: fiveyear survival results of the US multicenter, randomized, comparative study [C]. First Joint Annual Meeting of the American Society of Transplant Surgeons and the American Society of Transplantation. Chicago USA, 2000∶Abstract 10.
18. Pirsch JD,Miller J,Deierhoi MH, et al.A comparison of tacrolimus(FK506) and cyclosporine for immunosuppression after cadavceric renal transplantation [J]. Transplantaton, 1997; 63(7)∶977.
19. Martins L,Henriques AC,Dias L,et al.Conversion to Tacrolimus in caseproblem kidney transplant recipients under cyclosplrinebased immunosuppression [J]. Transplant Proc, 2000; 32(8)∶2636.
20. Thorp M, Demattos A,Bennett W,et al.The effect of conversion from cyclosporine to tacrolimus on gingival hyperplasia,hirsutism and cholesterol [J]. Transplantation, 2000; 69(6)∶1218.
21. Higgins RM,Hart P,Lam FT,et al.Conversion from tacrolimus to cyclosporine in stable renal transplant patients:safety,metabolic changes and pharmacokinetic comparison [J]. Transplantation,2000; 69(8)∶1736.
22. Papatheodoridis GV,O’Beirne J,Mistry P, et al.Mycophenolate mofetil monotherapy in stable liver transplant patients with cyclosporineinduced renal impairment: a preliminary report [J]. Transplantation, 1999; 68(1)∶155.
23. Vanrenterghem Y,Lebranchu Y,Hene R,et al.Doubleblind comparison of two corticosteroid regimens plus mycophenolate mofetil and cyclosporine for prevention of acute renal allograft rejection [J]. Transplantation, 2000; 70(9)∶1352.
24. Squifflet JP,Van Hooff JP,Vanrenterghem Y.The Benelux experience with the combination of tacrolimus and mycophenolate mofetil [J]. Transplant Proc, 1999; 31(7A)∶72s.
25. Morales JM, Andres A, Morales E,et al.Tacrolimus,Mycophenolate mofetil and corticosteroids as primary immunosuppression after renal transplantation at the hospital 12 De Octubre,Madrid [J]. Transplant Proc, 1999; 31(7A)∶75s.
26. Mihatsch MJ,Kyo M,Morozumi K,et al.The sideeffects of ciclosporineA and tacrolimus [J]. Clin Nephro, 1998; 49(6)∶356.
27. Lohmann R,Langrehr JM,Klupp J,et al.Infectious complications after orthotopic liver transplantation with different immunosuppressive induction regimens [J]. Transplant Proc, 2000; 32(3)∶537.
  1. 1. 陳實主編. 移植免疫學(xué) [M]. 第1版.武漢: 湖北科學(xué)技術(shù)出版社, 1998∶250~259.
  2. 2. Hutchinson IV, Bagnall W, Bryce P, et al.Differences in the mode of action of cyclosporine and FK506 [J]. Transplant Proc, 1998; 30(4)∶959.
  3. 3. Migita K, Origuchi T,Kawabe Y,et al.FK506 markedly enhances apoptosis of antigenstimulated peripheral T cells by downregulation of BclxL [J]. Transplantation, 1999; 68(7)∶1018.
  4. 4. Appleman LJ, Berezovskaya A, Grass I, et al.CD28 costimulation mediates T cell expansion via IL2independent and IL2dependent regulation of cell cycle progression [J]. J Immunol, 2000; 164(1)∶144.
  5. 5. Khanna AK,Hosenpud JD.Cyclosporine induces the expression of the cyclin inhibitor p21 [J]. Transplantation,1999; 67(9)∶1262.
  6. 6. Datto MB, Yu Y, Wang XF. Functional analysis of the transforming growth factor β responsive elements in the WAF1/Cipl/p21 promoter [J]. J Biol Chem, 1995; 270(48)∶28623.
  7. 7. Lee JI, Ganster RW, Geller DA, et al.Cyclosporine A inhibits the expression of costimulatory molecules on in vitrogenerated dendritic cells: association with reduced nuclear translocation of nuclear factor kappa B [J]. Transplantation, 1999; 68(9)∶1255.
  8. 8. Neuhaus P,Blumhardt G,Bechstein WO,et al.Comparison of FK506 and cyclosporinebased immunosuppression in primary orthotopic liver transplantation [J]. Transplantation, 1995; 59(1)∶31.
  9. 9. Wiesner RH.A longterm comparison of tacrolimus(FK506) versus cyclosporine in liver transplantation: a report of the United States FK506 Study Group [J]. Transplantation, 1998; 66(4)∶493.
  10. 10. 季曙明,殷立平,尹廣,等.他克莫司延緩移植腎功能衰竭進(jìn)程的臨床研究 [J]. 中華器官移植雜志, 2000; 21(5)∶291.
  11. 11. Wang T,Donahoe PK,Zervos AS.Specific interaction of typeⅠreceptors of the TGFβ family with the immunophilin FKBP12 [J]. Science, 1994; 265(5172)∶674.
  12. 12. Mohamed MA, Robertson H, Booth TA, et al. TGFβ expression in renal transplant biopsies:a comparative study between cyclosporinA and tacrolimus [J]. Transplantation, 2000; 69(5)∶1002.
  13. 13. Jain A, Mazariegos G, Kashyap R, et al. Comparative longterm evaluation of tacrolimus and cyclosporine in pediatric liver transplantation [J]. Transplantation, 2000; 70(4)∶617.
  14. 14. Greig PD.Early steroid withdrawal following liver transplantationtwoyear followup [C]. First Joint Annual Meeting of the American Society of Transplant Surgeons and the American Society of Transplantation.Chicago USA, 2000∶Abstract 1065.
  15. 15. Opelz G, Wujciak T, Ritz E.Association of chronic kidney graft failure with recipient blood pressure. [J]. Kidney Int, 1998; 53(1)∶217.
  16. 16. Stegall MD, Wachs ME, Everson G, et al.Prednisone withdrawal 14 days after liver transplantation with mycophenolate: a prospective trial of cyclosporine and tacrolimus [J]. Transplantation,1997; 64(12)∶1755.
  17. 17. Pirsch JD.Tacrolimus versus cyclosporine in kidney transplantation: fiveyear survival results of the US multicenter, randomized, comparative study [C]. First Joint Annual Meeting of the American Society of Transplant Surgeons and the American Society of Transplantation. Chicago USA, 2000∶Abstract 10.
  18. 18. Pirsch JD,Miller J,Deierhoi MH, et al.A comparison of tacrolimus(FK506) and cyclosporine for immunosuppression after cadavceric renal transplantation [J]. Transplantaton, 1997; 63(7)∶977.
  19. 19. Martins L,Henriques AC,Dias L,et al.Conversion to Tacrolimus in caseproblem kidney transplant recipients under cyclosplrinebased immunosuppression [J]. Transplant Proc, 2000; 32(8)∶2636.
  20. 20. Thorp M, Demattos A,Bennett W,et al.The effect of conversion from cyclosporine to tacrolimus on gingival hyperplasia,hirsutism and cholesterol [J]. Transplantation, 2000; 69(6)∶1218.
  21. 21. Higgins RM,Hart P,Lam FT,et al.Conversion from tacrolimus to cyclosporine in stable renal transplant patients:safety,metabolic changes and pharmacokinetic comparison [J]. Transplantation,2000; 69(8)∶1736.
  22. 22. Papatheodoridis GV,O’Beirne J,Mistry P, et al.Mycophenolate mofetil monotherapy in stable liver transplant patients with cyclosporineinduced renal impairment: a preliminary report [J]. Transplantation, 1999; 68(1)∶155.
  23. 23. Vanrenterghem Y,Lebranchu Y,Hene R,et al.Doubleblind comparison of two corticosteroid regimens plus mycophenolate mofetil and cyclosporine for prevention of acute renal allograft rejection [J]. Transplantation, 2000; 70(9)∶1352.
  24. 24. Squifflet JP,Van Hooff JP,Vanrenterghem Y.The Benelux experience with the combination of tacrolimus and mycophenolate mofetil [J]. Transplant Proc, 1999; 31(7A)∶72s.
  25. 25. Morales JM, Andres A, Morales E,et al.Tacrolimus,Mycophenolate mofetil and corticosteroids as primary immunosuppression after renal transplantation at the hospital 12 De Octubre,Madrid [J]. Transplant Proc, 1999; 31(7A)∶75s.
  26. 26. Mihatsch MJ,Kyo M,Morozumi K,et al.The sideeffects of ciclosporineA and tacrolimus [J]. Clin Nephro, 1998; 49(6)∶356.
  27. 27. Lohmann R,Langrehr JM,Klupp J,et al.Infectious complications after orthotopic liver transplantation with different immunosuppressive induction regimens [J]. Transplant Proc, 2000; 32(3)∶537.