Department of Emergency, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province, China.
Department of Rehabilitation Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province, China.
Pharm Biol. 2020 Dec;58(1):438-446. doi: 10.1080/13880209.2020.1762667.
Hypoxia-inducible factor-1α (HIF-1α)-induced genes can improve blood circulation. To investigate brain protective effect of recombinant adenovirus-mediated HIF-1α (AdHIF-1α) expression and its mechanism. 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 (10 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. 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 ( < 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) ( < 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 ( < 0.01) down-regulated and HSP90 up-regulated ( < 0.05) at mRNA and protein levels in AdHIF-1α group. 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.
缺氧诱导因子-1α（HIF-1α）诱导的基因可以改善血液循环。为了研究重组腺病毒介导的 HIF-1α（AdHIF-1α）表达的脑保护作用及其机制。雄性 SD 大鼠用于建立局灶性脑缺血再灌注（CIR）损伤模型，并随机分为正常、假手术、CIR、Ad 和 AdHIF-1α 组。Ad 或 AdHIF-1α（10 pfu/10 μL）分别给予 Ad 和 AdHIF-1α 组大鼠侧脑室。分析改良神经功能缺损评分（mNSS）、脑水含量（BWC）和脑梗死体积（CIV），并用脑组织进行 HE 染色。此外，用 qRT-PCR 和 Western blot 分析 caspase-3 和 HSP90 的表达。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）相比，AdHIF-1α 组在 72 h 时 mNSS 和 CIV 显著降低（mNSS，6.03 ± 0.61；CIV，0.11 ± 0.01）（ < 0.05）。随着再灌注时间的延长（6 h 至 72 h），所有大鼠的 BWC 逐渐增加，但 AdHIF-1α 组的增加明显小于 CIR（78.15 ± 0.16 至 89.74 ± 0.34）和 Ad 组（78.77 ± 0.35 至 89.71 ± 0.27）（ < 0.01）。CIR 后 72 h，AdHIF-1α 组神经元的病理变化明显更大。此外，AdHIF-1α 组 caspase-3 的表达下调（ < 0.01），HSP90 的表达上调（ < 0.05），mRNA 和蛋白水平均下调。HIF-1α 基因治疗对 CIR 大鼠模型具有神经保护作用。HIF-1α 可能是治疗缺血性脑损伤的候选基因。
