2-脱氧葡萄糖对脑缺血再灌注模型大鼠脑组织中葡萄糖调节蛋白78及天冬氨酸半胱氨酸蛋白酶-12的影响研究

Influence of 2-deoxyglucose on GRP78 and Caspase-12 in Rats with Cerebral Ischemia-reperfusion Injury

目的:探讨2-脱氧葡萄糖(2-DG)对脑缺血再灌注(IR)模型大鼠脑组织中葡萄糖调节蛋白78(GRP78)及天冬氨酸半胱氨酸蛋白酶-12(caspase-12)的影响。方法:取大鼠随机分为假手术组、模型组和2-DG组(2-DG100mg·kg-1),每组60只,后2组建立局灶性脑IR模型,假手术组行手术但不插入线栓。建模前7d开始给药,每天1次,连续7d,考察建模后3、6、12、24、48h各组大鼠海马CA1区细胞凋亡情况(阳性细胞率)、GRP78和caspase-12蛋白及其mRNA的表达情况。结果:与假手术组比较,模型组和2-DG组阳性细胞率、GRP78和caspase-12蛋白及其mRNA表达均明显升高(P均<0.01);与模型组比较,2-DG组阳性细胞率、cas-pase-12蛋白及其mRNA表达明显降低,GRP78蛋白及其mRNA表达明显升高(P<0.05或P<0.01)。结论:2-DG可能通过上调GRP78和下调caspase-12的表达来预防脑IR损伤。

OBJECTIVE： To investigate the influence of 2-deoxyglucose （2-DG） on glucose-regulated protein （GRP） 78 and caspase-12 in rats with cerebral ischemia-reperfusion injury. METHODS： Rats were randomly divided into sham operation group, model group and 2-DG group （2-DG 100 mg·kg^-1） with 60 rats in each group. IR model was induced in the latter two groups. In sham operation group, operation was performed while occlusion not. Those groups were given medicine once a day 7 days before modeling. Cell apoptosis （positive cell rate）, the expressions of GRP78 and caspase-12 protein and mRNA of hippocampus CA1 area were detected 3, 6, 12, 24, 48 h after modeling. RESULTS： Compared with sham operation group, positive cell rate, the expressions of GRP78 and caspase-12 protein and mRNA of hippocampus CA1 area in IR group and 2-DG group increased significantly （P〈0.01）. Compared with IR group, positive cell rate, the expressions of caspase-12 protein and mRNA of hippocampus CA1 area decreased significantly while the expressions of GRP 78 protein and mRNA increased significantly （P〈0.05 or P〈0.01） in 2-DG group. CONCLUSIONS： 2-DG might prevent cerebral IR injury by up-regulating GRP78 expression and down-regulating cas- pase-12 expression.