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卢一平, M.Z. Liang, Y.P. Lu, F. Nan, Q. Yu, Y.P. Qin, and Y.G. Zou
Transplantation Proceedings, 36, 2065-2067 (2004),-0001,():
-1年11月30日
MYCOPHENOLIC acid (MPA) is the active metabolite of mycophenolate mofetil (MMF). Because of its immunosuppressive properties, the drug has now been widely used in immunosuppressive protocols after solid organ transplantation and for autoimmune diseases. The purpose of this study was to investigate the pharmacokinetics of MPA after single and multiple oral administrations of the pro-drug of MPA (MMF), in Chinese renal transplant recipients.
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卢一平, Y.P. Lu, B. Lin, M.Z. Liang, L. Wang, F. Nan, Q. Yu, and K.S. Tang
Transplantation Proceedings, 36, 2079-2081 (2004),-0001,():
-1年11月30日
MYCOPHENOLATE mofetil (MMF) is widely used in organ transplantation combined with other immunosuppressants to prevent acute rejection. 1-3 Because MMF can produce side effects, especially hematological and/or gastrointestinal toxicity, 1-5 therapeutic monitoring is becoming mandatory. Furthermore, there is no study to show the characteristics of MMF pharmacokinetics (PK) in Chinese patients. This study was designed to investigate the relationship between clinical events and the PK of mycophenolic acid (MPA) in Chinese kidney transplant recipients.
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卢一平, R. Gao, Y. Lu, Y.P. Xin, X.H. Zhang, J. Wang, and Y.P. Li
Transplantation Proceedings, 38, 2154-2157 (2006),-0001,():
-1年11月30日
Objective. This study investigated the effects of various immunosuppressants on chronic allograft nephropathy (CAN) by affecting transforming growth factor-β(TGF-β) and Smads signal pathway. Methods. Vascular smooth muscle cells (VMSC) from rat aorta were incubated for 6 or 12 hours with various immunosuppressants. Cyclosporine (CsA) (3μg/mL), FK506 (1μg/mL), mycophenolate mofetil (MMF) (0.3μg/mL), rapamycine (Rapa) (10μg/mL), CsA (1μg/mL/MMF 0.3μg/mL). We used the Sprague-Dawly Wistar rat accelerated kidney sclerosis model. Before transplantation, the kidney was preserved 1 hour in 0℃ to 4℃ heparin sodium chloride solution to reinforce the cold ischemia injury. The rats were divided into eight groups (each group n式8): group A, pseudo-OP; group B, isotransplantation; group C, CsA 6mg/kg•d; group D, FK506 0.15mg/kg•d; group E, MMF 20mg/kg•d; group F, Rapa 0.8mg/kg•d; group G, CsA 3mg/kg•d; MMF 20mg/kg•d. The serum creatinine levels and pathological changes, according to the Banff scheme, were observed at 2, 4, 6, 8 and 12 weeks posttransplantation. Immunohistochemistry and quantitative fluorescence polymerase chain reactions were used to end localize and quantitate the expression of TGF- 1 and Smad 2, 3, 7 in VMSC and in the transplanted kidney. Results. CsA and FK506 stimulated gene expression and protein production of TGF-β1, smad2, and smad3, but inhibited expression of smad7 both in VSMC and in the transplanted kidney. In contrast, MMF and Rapa down-regulated gene expression and protein production of TGF-β1, smad2, 3 while up-regulating expression of smad7. There was no significant difference between the CsA group and the FK506 group, as well as the MMF group and the Rapa group. The group treated with CsAβMMF was similar to the MMF and the Rapa groups. Conclusion. Our study suggested that various immunosuppresants affected differentially TGF-β1 and Smads signal pathways in rat VSMC and kidney grafts. CsA and FK506 can cause CAN, owing to up-regulated expression of smad2 and smad3, and down-regulation of smad7 expression. MMF and Rapa can prevent the CAN progression, because of down-regulation of the expression of smad2 and smad3, with increased smad7 production.
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