热休克蛋白干预脑缺血缺氧模型大鼠神经功能及脑组织中血红素加氧酶1蛋白的表达

Effect of heat shock protein on neurological function and heme oxygenase-1 protein expression in a rat model of cerebral ischemia and hypoxia

背景:脑缺血缺氧可引发一系列复杂的级联反应,因其发病机制复杂,至今无理想的治疗药物。目的:探究热休克蛋白对脑缺血缺氧大鼠血红素氧化酶1蛋白表达及神经功能的影响。方法:将30只大鼠随机分为假手术组、脑缺血缺氧模型组、热休克蛋白70组,每组10只。后两组制备脑缺血缺氧大鼠模型;假手术组大鼠不进行结扎;热休克蛋白70组在造模基础上给予尾部注射0.5 m L重组腺病毒v Ad-HSP70悬液,1次/d,给药3 d。给药结束后比较3组大鼠的神经功能、氧化指标、大鼠脑组织的含水量及梗死面积;苏木精-伊红染色观察3组大鼠脑组织形态;Western blot检测大鼠脑组织中血红素氧化酶1蛋白的表达。结果与结论:(1)与假手术组相比,脑缺血缺氧模型组大鼠的神经功能评分显著降低,热休克蛋白70组大鼠的神经功能评分显著升高(P <0.05);(2)脑缺血缺氧模型组大鼠的脑积水量和梗死面积明显大于假手术组(P <0.05);并且脑缺血缺氧模型组大鼠的脑组织发生显著变化,细胞分布散乱,且数量缺失明显增多,坏死细胞较多;(3)与脑缺血缺氧模型组相比,热休克蛋白70组大鼠的脑积水量和梗死面积显著减小,且脑组织形态明显改善(P <0.05);(4)脑缺血缺氧模型组大鼠脑组织血红素氧化酶1蛋白表达显著低于假手术组;与脑缺血缺氧模型组相比,热休克蛋白70组大鼠脑组织中血红素氧化酶1蛋白表达水平显著升高(P <0.05);(5)提示热休克蛋白可有效降低缺血缺氧大鼠的氧化应激损伤,改善神经功能,缩小脑梗死面积及脑积水含量,其作用机制可能与提高血红素氧化酶1蛋白表达有关。

BACKGROUND:Cerebral ischemia and hypoxia can trigger a series of complex cascade reactions.Due to its complex pathogenesis,there is no ideal drug for the treatment of cerebral ischemia and hypoxia.OBJECTIVE:To investigate the effects of heat shock proteins on heme oxygenase-1 protein expression and neurological function in rats with cerebral ischemia and hypoxia.METHODS:Thirty rats were randomly divided into sham-operated group,model group,heat shock protein 70 group,with 10 rats in each group.Animal models of cerebral ischemia and hypoxia were made in the latter two groups.Rats in the sham-operated group were given no ligation.After modeling,the heat shock protein 70 group was given tail injection of recombinant adenovirus vAd-HSP70 suspension(0.5 mL),once a day for 3 days.The neurological function,oxidation index,water content and infarct area of the three groups were compared.Hematoxylin-eosin staining was used to observe the morphology of the rat brain.Western blot was used to detect the expression of heme oxygenase-1 protein in the rat brain.RESULTS AND CONCLUSION:Compared with the sham-operated group,the neurological function scores in the model group were significantly decreased,while those in the heat shock protein 70 group were significantly increased(P <0.05).The brain water content and infa rct area of rats in the model group were significantly higher than those in the sham-operated group(P <0.05),and the brain tissue of rats in the model group had significant changes,with scattered cell distribution,significant loss of cells and increased number of necrotic cells.Compared with the model group,the brain water content and infarct area were significantly decreased in the heat shock protein 70 group(P <0.05) and the morphology of brain tissue was significantly improved(P <0.05).The expression of heme oxygenase-1 protein in the brain tissue was significantly lower in the model group than the sham-operated group,but was significantly higher in the heat shock protein 70 group than the model group(P <0.05),To conclude,heat shock proteins can effectively reduce oxidative stress damage,improve neurological function,and decrease cerebral infarct area and brain water content in the rat model of cerebral ischemia and hypoxia.Its mechanism of action may be related to the increase of heme oxygenase-1 protein expression.