Protective effect of 2-deoxy-D-glucose on the brain tissue in rat cerebral ischemia-reperfusion models by inhibiting Caspase-apoptotic pathway.
We observed the effect of 2-deoxy-D-glucose (2-DG) on the brain tissue in rat cerebral ischemia-reperfusion (I/R) and explored its mechanism. After observing the effect of 2-DG on endoplasmic reticulum stress (ERS), rats were randomly divided into sham-operation 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 (3h, 6h, 12h, 24h and 48h) 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 cleaved-caspase-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, cleaved-caspase-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 cleaved-caspase-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 cleaved-caspase-9 and cleaved-caspase-3, which blocks the apoptotic pathway.
Graduate School, Jinzhou Medical University, Jinzhou, China.
He-Ming
HM
Min
Department of Neurology, the First Affiliated Hospital, Jinzhou Medical University, Jinzhou, China.|Department of Cell Biology, Basic Medical College of Jinzhou Medical University, Jinzhou, China.
Yan
Y
Wang
Department of Neurology, the First Affiliated Hospital, Jinzhou Medical University, Jinzhou, China.
Da-Yong
DY
Ren
Department of Neurology, the First Affiliated Hospital, Jinzhou Medical University, Jinzhou, China.
Xue
X
Cheng
Department of Neurology, the First Affiliated Hospital, Jinzhou Medical University, Jinzhou, China.
Jian
J
Li
Department of Neurology, the First Affiliated Hospital, Jinzhou Medical University, Jinzhou, China.
Xing-Qian
XQ
Jiang
Department of Neurology, the First Affiliated Hospital, Jinzhou Medical University, Jinzhou, China. minlianquiu@163.com.
Lian-Qiu
LQ
Min
Department of Cell Biology, Basic Medical College of Jinzhou Medical University, Jinzhou, China.
Cui-Fen
CF
Bao
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology*; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D020287:In Situ Nick-End Labeling; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology*
D018696:Neuroprotective Agents; D003847:Deoxyglucose; D020169:Caspases