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.

IT HAS been well proven that donor-specific antigens (DS-Ags) could induce immunologic tolerance of recipients and prolong allograft survival. But the detailed mechanisms are still unclear. The effect of the DS-Ags is influenced by some factors, particularly the species, the histocompatibility barries, the different sources of the DSAgs, the different pathways that the DS-Ags were given, the dose and timing of DS-Ags infusion, the immunoreactivity of the recipient to DS-Ags, etc. In this study, different DS-Ags and different pathways through which the DS-Ags were given were compared.

Purposes. To compare the pharmacokinetic parameters of mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG) after single and multiple oral administration of mycophenolate mofetil (MMF) in Chinese renal transplant patients with those of recipients in other countries. Methods. Twelve Chinese renal transplant patients after an overnight fast received a single 1g dose of MMF before renal transplantation. Thereafter the patients received 1g MMF twice a day up to and on the day 12 after renal transplantation. The concentrations of MPA and MPAG were simultaneously measured by RP-HPLC. The concentration-time data were examined with Drug and Statistics pharmacokinetic software. Using paired samples t test (self-contrast) with SPSS statistical software (a=0.05), we compared the pharmacokinetic parameters between single and multiple doses. Results and discussions. The MPA concentration-time profiles were fitted to a twocompartment open model; MPAG concentration-time profiles were fitted to a singlecompartment open model. Compared with the literature reports, the main pharmacokinetic parameters of MPA and MPAG shown by our research revealed some differences. The parent drug MMF was undetectable in plasma during oral administration. A secondary peak of MPA occurred at 6 to 10 hours, which was attributed to enterohepatic recirculation. There was significant variation in MPA and MPAG plasma concentrationtime data among subjects. It is suggested that therapeutic drug monitoring should be applied for dosage optimization.

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.

ONE OF the serious problems in allogenic clinical transplantation is the shortage of grafts. The pig is now widely accepted as the most appropriate candidate for xenotransplantation.1 It is very important to establish a large animal model to mimic pig-to-human xenotransplantation and to evaluate the donor-recipient interaction during the whole course in vivo. Our previous study showed that human bone marrow and spleen cells could survive in recipient pig for a long time after transplant. In this study, human spleen or spleen tissue was transplanted into pig to establish a higher level of chimerism. Therefore, it is possible to observe the interaction of human against pig, and it might be possible to develop xenogenic graft-versushost disease (xGVHD).