INVESTIGADORES
CHULUYAN Hector Eduardo
artículos
Título:
Preconditioning donor with a combination of tacrolimus and rapamacyn to decrease ischaemiareperfusion injury in a rat syngenic kidney transplantation model
Autor/es:
CICORA F; ROBERTI, J; VASQUEZ, D; GUERRIERI, D; LAUSADA, N; CICORA, P; PALTI, G; CHULUYAN, E; GONZALEZ, P; STRINGA, P; RAIMONDI, C
Revista:
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Lugar: Londres; Año: 2011 vol. 167 p. 169 - 177
ISSN:
0009-9104
Resumen:
Reperfusion injury remains one of the major problems in transplantation.
Repair from ischaemic acute renal failure (ARF) involves stimulation of
tubular epithelial cell proliferation. The aim of this exploratory study was to
evaluate the effects of preconditioning donor animals with rapamycin and
tacrolimus to prevent ischaemiareperfusion (I/R) injury. Twelve hours
before nephrectomy, the donor animals received immunosuppressive drugs.
The animals were divided into four groups, as follows: group 1 control: no
treatment; group 2: rapamycin (2 mg/kg); group 3 FK506 (0, 3 mg/kg); and
group 4: FK506 (0, 3 mg/kg) plus rapamycin (2 mg/kg). The left kidney was
removed and after 3 h of cold ischaemia, the graft was transplanted. Twentyfour
hours after transplant, the kidney was recovered for histological analysis
and cytokine expression. Preconditioning treatment with rapamycin or tacrolimus
significantly reduced blood urea nitrogen and creatinine compared
with control [blood urea nitrogen (BUN): P < 0·001 versus control and creatinine:
P < 0·001 versus control]. A further decrease was observed when rapamycin
was combined with tacrolimus. Acute tubular necrosis was decreased
significantly in donors treated with immunosuppressants compared with the
control group (P < 0·001 versus control). Moreover, the number of apoptotic
nuclei in the control group was higher compared with the treated groups
(P < 0·001 versus control). Surprisingly, only rapamycin preconditioning
treatment increased anti-apoptotic Bcl2 levels (P < 0·001). Finally, inflammatory
cytokines, such as tumour necrosis factor (TNF)-a and interleukin
(IL)-6, showed lower levels in the graft of those animals that had been pretreated
with rapamycin or tacrolimus. This exploratory study demonstrates
that preconditioning donor animals with rapamycin or tacrolimus improves
clinical outcomes and reduce necrosis and apoptosis in kidney I/R injury.