Protective effect of 2-deoxy-D-glucose on the brain tissue in rat cerebral ischemia-reperfusion models by inhibiting caspase-apoptotic pathway
He-ming Min1, Yan Wang2,3, Da-yong Ren2, Xue Cheng2, Jian Li2, Xing-qian Jiang2, Lian-qiu Min2 and Cui-fen Bao3
1Graduate School, 2Department of Neurology, the First Affiliated Hospital, Jinzhou Medical University and 3Department of Cell Biology, Basic Medical College of Jinzhou Medical University, Jinzhou, China
Offprint requests to: Lian-qiu Min and Cui-fen Bao, No.2, Section 5, Guta District, Jinzhou 121001, China. e-mail: minlianqiu@163.com
Summary. 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 (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 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. Histol Histopathol 32, 57-67 (2017)
Key words: 2-deoxy-D-glucose, Endoplasmic reticulum stress, Cerebral ischemia-reperfusion injury, Glucose regulated protein 78, Cleaved-caspase-9, Cleaved-caspase-3
DOI: 10.14670/HH-11-770