[Study of R2* value to evaluate regulation of liver regeneration by hepatic warm ischemia-reperfusion injury after partial hepatectomy in rabbits].

Objective: To investigate the effect of R2* value on the evaluation of different degrees of hepatic warm ischemia-reperfusion injury (WIRI) and liver regeneration after partial hepatectomy in rabbits. Methods: Thirty healthy adult male New Zealand White rabbits were randomly divided into five groups. Hepatic caudal lobectomy was performed in both the control and the warm ischemia time-dependent variation group. After reperfusion, routine MRI and BOLD MRI scans were performed for each group at 6 h, 3 d, 7 d, 14 d and 30 d, respectively, and then R2* value and liver regeneration rate (LRR) were measured and calculated. After 30 days of scanning, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), myeloperoxidase (MPO), tumor necrosis factor - α (TNF - α), interleukin-6 (IL-6) and proliferating cell nuclear antigen (PCNA) were detected in frozen rabbit liver tissues, and the pathological sections were collected. Repeated measures analysis of variance was used to evaluate the changes of R2* value, LRR and its influencing factors at different follow-up time and warm ischemia time in each group. Pearson's or Spearman's correlation analysis was used to evaluate the correlation of R2* value with LRR and various biochemical indexes. Results: The interaction between different follow-up time and warm ischemia time (F = 24.600, P < 0.001) and the single effect of the both on the R2* value had statistically significant difference (P < 0.05). The interaction of different follow-up time and different warm ischemia time had no effect on LRR, and the difference was not statistically significant (F = 0.925, P = 0.528), but the difference in the main effect of the both on LRR was statistically significant (P < 0.05). At the same follow-up time, except for the 40-min ischemia group, the R2* values ​​were significantly positively correlated with LRR (3, 7, 14, 30 days after operation, r = 0.510, 0.681, 0.612, 0.541 respectively, P < 0.05). At the same warm ischemia time, the R2* value were significantly negatively correlated with LRR (3, 7, 14, 30 and 40 days after operation, r = - 0.800, -0.852, -0.893, -0.648, -0.853, respectively, P < 0.05). There was no correlation between R2 * value and biochemical indexes at 30 days after operation (P > 0.05). Conclusion: The R2* value may be used for noninvasive and quantitative evaluation of microstructural changes of WIRI and affect liver regeneration after partial hepatectomy in rabbits. A certain degree of WIRI (≤30 min) after partial hepatectomy can promote liver regeneration in rabbits. Furthermore, as the warm ischemia time prolongs, the promoting effect becomes more pronounced, and if the warm ischemic time exceeds 30 minutes, the promoting effect is significantly reduced.

Sirolimus did not affect CD4(+)CD25(high) forkhead box p3(+)T cells of peripheral blood in renal transplant recipients.

INTRODUCTION: To achieve a true state of allo-tolerance is one of the ultimate goals in transplantation. Many studies suggest that CD4(+)CD25(high) T regulatory cells (Tregs) have a crucial role to down-regulate the immune response to allo-antigens. In this study, we investigated the possible influence of immunosuppressive therapy, including sirolimus (SRL) and calcineurin inhibitors (CNIs, tacrolimus, or cyclosporine), on the level of Tregs in renal allograft recipients. MATERIALS AND METHODS: We assessed 88 renal transplant recipients with stable renal function for at least 2 years, dividing them into 2 groups: SRL-treated (n = 28) or CNIs-treated (n = 29 tacrolimus and n = 31 cyclosporine). Thirty-eight age-matched healthy subjects (HS) served as normal controls. We examined the expression of CD4, CD25, and forkhead box p3 (Foxp3) in peripheral blood mononuclear cells. Flow cytometry was performed with data analysis using Cell Quest software. The 5-year graft survivals were correlated with Tregs content. RESULTS: CNIs significantly decreased the percentage of Tregs compared with the HS and SRL groups (P < .01). The percentage of Tregs in the SRL group was not significantly different from that among HS. The ratio of CD4(+)CD25(high)Tregs to CD4(+) T cells was 0.88% (0.28-1.42%), 1.15% (0.57-1.48%), and 0.21% (0.11-0.29%) among the SRL, HS, and CNIs cohorts respectively (SRL vs CNIs, P = .000165; SRL vs HS, P = .258; CNIs vs HS, P = .00030). Foxp3 was expressed in >95% of CD4(+)CD25(high) T cells versus <20% among CD4(+)CD25(low) T cells and not at all in CD4(+)CD25(-) T cells. Five-year graft survivals showed no difference between the 2 cohorts (P > .05), and was not correlated with the level of CD4(+)CD25(high) T cells. CONCLUSIONS: Various immunosuppressive therapies may show different roles in tolerance induction. The present findings suggest that SRL facilitates the induction of CD4(+)CD25(high) T cells, whereas CNIs hamper their development. Graft success for 5 years did not correlate with the level of these putative regulatory cells.