摘要
目的 探究新型氧氮自由基HPN对脑缺血再灌注损伤模型大鼠中缺氧相关蛋白表达的影响。方法 采用随机数字表法将60只雄性SD大鼠平均分为MCAO/R模型组、假手术组、HPN低、中、高剂量组(100、150、200 mg/kg),每组12只,模型组及HPN给药组采用改良的Longa线栓法构建右侧大脑中动脉阻塞再灌注(MCAO/R)模型,以仅分离右侧颈内动脉的假手术大鼠为对照,再灌注24 h后进行神经功能缺损症状评分;TTC染色测定脑梗死体积;HE染色观察各组脑区半暗带区病理变化;实时定量PCR检测大脑皮层中缺氧相关蛋白HIF-1a和VEGF的基因表达;Western blot检测大脑皮层中缺氧相关蛋白HIF-1a和VEGF的表达。结果 与MCAO/R模型组相比,HPN给药组中大鼠的神经功能得到明显改善(P<0.05),脑梗死体积明显减少,大脑皮层中HIF-1a和VEGF蛋白及基因表达明显降低(P<0.01)。与HPN低剂量组相比,HPN中、高剂量组大脑皮层中HIF-1a和VEGF蛋白及基因表达明显增加(P<0.05)。结论 新型氧氮自由基HPN在脑缺血再灌注损伤模型大鼠中具有显著的神经保护作用,且随着HPN给药剂量的增加,对神经保护作用越明显,并显著调节缺氧相关蛋白HIF-1a和VEGF的表达。
Objective To Explore the effect of HPN on the expression of hypoxia-related proteins in cerebral ischemia-reperfusion injury in rats.Methods Sixty male SD rats were randomly divided into a sham-operated group,a model group,and HPN low-dose,medium-dose,and high-dose groups(100,150,200 mg/kg,respectively),with 12 rats in each group.The model group and the HPN administration group were constructed as a right middle cerebral artery occlusion/reperfusion(MCAO/R)model by using the modified Longa wire bolus method,and a sham-operated rat with the isolation of the right internal carotid artery only was used as a control.The subsequent experiments were carried out 24 hours after reperfusion:Neurological deficit symptom was scored;TTC staining was used to determine the volume of cerebral infarction;HE staining was used to observe the pathological changes in the semi-dark zone area of the brain regions of each group.Real-time quantitative PCR(Real-Time PCR)was used to detect the gene expression of hypoxia-associated proteins HIF-1αand VEGF in the cerebral cortex;Western blot detected the protein expression of hypoxia-associated proteins HIF-1αand VEGF in the cerebral cortex.Results Compared with the model group,the HPN administration group significantly improved neurological deficits(P<0.05),reduced the volume of cerebral infarction,and significantly reduced the expression of HIF-1αand VEGF proteins and genes in the cerebral cortex(P<0.01),thus protecting against cerebral ischemia/reperfusion injury.Compared with the low-dose group of HPN,the cerebral cortex of the medium-and high-dose groups of HPN showed significantly increased HIF-1αand VEGF protein and gene expression(P<0.05).Conclusion HPN had a significant neuroprotective effect in cerebral ischemia-reperfusion injury model rats,and the neuroprotective effect was more obvious with the increase of HPN administration dose,which significantly regulated the expression of hypoxia-related proteins HIF-1αand VEGF.
作者
梁恒
钱军
刘志鹏
罗红波
Liang Heng;Qian Jun;Liu Zhipeng;Luo Hongbo(Department of Neurology,the Fifth Affiliated Hospital of Zunyi Medical University,Zhuhai Guangdong 519100,China)
出处
《遵义医科大学学报》
2024年第3期230-236,245,共8页
Journal of Zunyi Medical University
基金
贵州省科技计划项目[NO:黔科合支撑(2020)4Y128]。
