Abstract Context: Hypoxia-inducible factor-1α (HIF-1α)-induced genes can improve blood circulation. Objective: To investigate brain protective effect of recombinant adenovirus-mediated HIF-1α (AdHIF-1α) expression and its mechanism. Materials and methods: Male SD rats were used to establish focal cerebral ischaemia-reperfusion (CIR) injury models and randomly divided into normal, sham, CIR, Ad and AdHIF-1α groups. Ad or AdHIF-1α (108 pfu/10 µL) were administered into lateral ventricle of rats in Ad and AdHIF-1α groups. Modified neurological severity score (mNSS), brain water content (BWC) and cerebral infarct volumes (CIVs) were analyzed, and HE staining was performed using the brain tissues. Furthermore, the expression of caspase-3 and HSP90 was analyzed using qRT-PCR and Western blotting. Results: Compared to CIR (mNSS, 8.52 ± 0.52; CIV, 0.22 ± 0.01) and Ad groups (mNSS, 8.83 ± 0.41; CIV, 0.22 ± 0.02), mNSS and CIV were significantly decreased in AdHIF-1α group (mNSS, 6.03 ± 0.61; CIV, 0.11 ± 0.01) at 72 h (p < 0.05). With prolonged reperfusion time (6 h to 72 h), BWC of all rats increased gradually, although the increase was markedly less in AdHIF-1α group (78.15 ± 0.16 to 87.01 ± 0.31) compared to that in CIR (78.77 ± 0.60 to 89.74 ± 0.34) and Ad groups (78.77 ± 0.35 to 89.71 ± 0.27) (p < 0.01). There were significantly greater pathological changes in the neurons in AdHIF-1α group at 72 h following CIR. Furthermore, expression of caspase-3 (p < 0.01) down-regulated and HSP90 up-regulated (p < 0.05) at mRNA and protein levels in AdHIF-1α group. Discussion and conclusions: HIF‑1α gene therapy is neuroprotective towards the CIR rat model. HIF-1α may be a candidate gene for the treatment of ischaemic brain injury.

中文翻译：

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重组腺病毒对缺氧诱导因子1α基因治疗大鼠脑缺血再灌注损伤的保护作用

摘要背景：缺氧诱导因子-1α (HIF-1α) 诱导的基因可以改善血液循环。目的：探讨重组腺病毒介导的HIF-1α（AdHIF-1α）表达的脑保护作用及其机制。材料与方法：采用雄性SD大鼠建立局灶性脑缺血再灌注(CIR)损伤模型，随机分为正常组、假手术组、CIR组、Ad组和AdHIF-1α组。Ad 或 AdHIF-1α (108 pfu/10 µL) 分别注入 Ad 和 AdHIF-1α 组大鼠的侧脑室。分析了修正的神经严重程度评分 (mNSS)、脑含水量 (BWC) 和脑梗塞体积 (CIV)，并使用脑组织进行 HE 染色。此外，使用 qRT-PCR 和蛋白质印迹分析了 caspase-3 和 HSP90 的表达。结果：与 CIR (mNSS, 8.52 ± 0.52; CIV, 0. 22 ± 0.01) 和 Ad 组 (mNSS, 8.83 ± 0.41; CIV, 0.22 ± 0.02), AdHIF-1α 组 (mNSS, 6.03 ± 0.61; CIV, 0.11 ± 0.01 (p) 时 mNSS 和 CIV 显着降低) < 0.05)。随着再灌注时间的延长（6 h～72 h），所有大鼠的BWC逐渐增加，但AdHIF-1α组的增加幅度（78.15±0.16～87.01±0.31）明显低于CIR组（78.77±0.60～89.74） ± 0.34）和广告组（78.77 ± 0.35 至 89.71 ± 0.27）（p < 0.01）。CIR后72 h，AdHIF-1α组神经元的病理变化明显更大。此外，在 AdHIF-1α 组中，在 mRNA 和蛋白质水平上，caspase-3 的表达（p < 0.01）下调，HSP90 的表达上调（p < 0.05）。讨论和结论：HIF-1α 基因治疗对 CIR 大鼠模型具有神经保护作用。