222 462

Cited 0 times in

Effects of various durations of post-treatment with trimetazidine against ischemia-reperfusion : early and long-term effects in a rat kidney model

Other Titles
 다양한 투여 기간의 trimetazidine이 허혈-재관류 손상에 미치는 효과 :쥐 신장 모델에서 단기 및 장기 효과 
 College of Medicine (의과대학) 
 Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) 
Issue Date
Dept. of Medicine/박사
Acute kidney injury (AKI) is a well-known risk factor for poor prognosis in hospitalized
patients and believed to be often the consequence of ischemia-reperfusion (I/R) injury. The rats were euthanized 5 days or 8 weeks after I/R injury. The effect of post I/R treatment
with TMZ was determined using different variables: renal function (serum blood urea nitrogen
[BUN] and creatinine), renal histologic change including apoptotic cell death and fibrosis, and
related signaling proteins including hypoxia inducible factor (HIF)-1α, vascular endothelial
growth factor (VEGF), phosphorylated-Akt (P-Akt), endothelial nitric oxide synthase (eNOS),
Bcl-2, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs).
Post I/R treatment with TMZ significantly reduced serum levels of BUN and creatinine,
apoptotic cell death through up-regulation of HIF-1α-VEGF and P-Akt/eNOS, and Bcl-2 related
apoptotic signaling pathways 24 hr after renal I/R injury. Although serum levels of BUN and
creatinine recovered to baseline values, post I/R treatment with TMZ reduced renal tubular cell
necrosis and apoptosis via up-regulation of HIF-1α-VEGF, P-Akt/eNOS, and TIMPs,
attenuation of MMPs activities, and alteration of the ratio of Bax for Bcl-2 at 5 days after renal
I/R injury regardless of the treatment protocol. Post I/R treatment with TMZ, however, did not
suppress the progression of renal fibrosis and expression of related signal pathways, 8 weeks
after renal I/R injury.
These results indicate that post I/R treatment with TMZ has beneficial effect on renal
protection against I/R injury at early and intermediate period, while it failed to inhibit the longterm
renal fibrotic change.
Trimetazidine (TMZ, 1 - [2, 3, 4 - trimethoxybenzyl] piperazine, dihydrochloride), an antiischemic
agent used for decades, has a theoretical potential to reduce I/R injury through
modulations of various cell survival pathways. Yet, the majority of studies including clinical
studies have concentrated on the early effects of TMZ pre-treated before I/R injury, limiting its
clinical applicability. The aim of this study was to elucidate the effects of various durations of
TMZ administered after renal I/R injury on renal recovery in long-term as well as short-term
aspects with the evaluation of relevant signaling pathways in rats.
In short-term study, Sprague-Dawley (SD) rats were randomly assigned to four groups: Sham,
untreated control I/R (IRC), TMZ treatment before I/R (TMZ-pre), TMZ treatment after I/R
(TMZ-post). TMZ (3 mg/kg, intraperitoneally) was administered 1 hr before ischemia (pre) or
upon reperfusion (post). All rats except in the Sham group underwent left side nephrectomy and
the right renal pedicle was clamped for 45 min and then reperfused for 24 hr when the rats were
euthanized for analysis. In intermediate and long-term studies, rats were randomly assigned to
four groups: Sham, IRC, TMZ post-treatment after I/R (TMZ-single), daily TMZ post-treatment
after I/R (TMZ-daily). TMZ (3 mg/kg, intraperitoneally) was administered once immediately
upon reperfusion (TMZ-single), or administered once a day for a scheduled period (TMZ-daily).
Files in This Item:
TA02070.pdf Download
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 3. Dissertation
Yonsei Authors
Park, Jin Ha(박진하) ORCID logo https://orcid.org/0000-0002-1398-3304
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.