Publication: Protective effect of 2-deoxy-D-glucose on the brain tissue in rat cerebral ischemia-reperfusion models by inhibiting caspase-apoptotic pathway
Authors
Min, He-ming ; Wang, Yan ; Ren, Da Yong ; Cheng, Xue ; Li, Jian ; Jiang, Xing qian ; Min, Lian qiu ; Bao, Cui fen
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Publisher
Universidad de Murcia. Departamento de BiologĂa Celular e HistologĂa
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DOI
DOI: 10.14670/HH-11-770
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info:eu-repo/semantics/article
Description
Abstract
We observed the effect of 2-deoxy-D-glucose
(2-DG) on the brain tissue in rat cerebral ischemiareperfusion (I/R) and explored its mechanism. After
observing the effect of 2-DG on endoplasmic reticulum
stress (ERS), rats were randomly divided into shamoperation group, I/R group and I/R+2-DG group (each
group with 60 rats). I/R models were prepared by middle
cerebral artery occlusion. In I/R+2-DG group, each rat
was given intraperitoneal 2-DG of 100 mg/kg once a day
for 7 days before brain ischemia. According to different
time points (3 h, 6 h, 12 h, 24 h and 48 h) after I/R, each
group was divided into 5 subgroups (each subgroup with
12 rats). Nerve cell apoptosis, and the expressions of
mRNA and protein of glucose regulated protein 78
(GRP78), cleaved-caspase-9 and cleaved-caspase-3 were
determined with TUNEL, Western blotting and RT-PCR,
respectively, in rat cerebral hippocampal CA1 area at
each time point. TUNEL-positive cells were
significantly less in I/R+2-DG group than in I/R group at
each time point (all P<0.01). In I/R and I/R+2-DG
groups, the expressions of mRNA and protein of GRP78
reached the maximum 12 h after I/R, and cleavedcaspase-9 and cleaved-caspase-3 reached the maximum
24 h after I/R. Compared with sham-operation group, the
expressions of mRNA and protein of GRP78, cleavedcaspase-9 and cleaved-caspase-3 were all significantly
increased (all P<0.01) in I/R and I/R+2-DG groups.
However, the expressions of mRNA and protein of
GRP78 were significantly higher in I/R+2-DG group
than in I/R group (all P<0.05), but the expressions of
mRNA and protein of cleaved-caspase-9 and cleavedcaspase-3 were all significantly lower in I/R+2-DG
group than in I/R group (all P<0.05). We conclude that
2-DG has a neuroprotective effect on the brain tissue in
rat cerebral ischemia-reperfusion models. The
mechanism may be that 2-DG starts ERS followed by
up-regulation of mRNA and protein of GRP78 and
down-regulation of mRNA and protein of cleavedcaspase-9 and cleaved-caspase-3, which blocks the
apoptotic pathway.
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Citation
Histology and Histopathology, Vol.32, nÂş1, (2017)
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