Hypoxia-inducible factor 1 alpha is involved in brain injury/protection in rats with acute cerebral infarction

doi:10.12307/2021.294

Abstract

Abstract: BACKGROUND: Acute cerebral infarction indicates hypoxic-ischemic necrosis in brain tissue, which has become the first cause of death in China. Hypoxia-inducible factor-1α plays a dual role on the occurrence and development of cerebral infarction. Therefore, it is particularly important to use its inhibitor at immediate time in clinical therapy.
OBJECTIVE: To investigate the effects of hypoxia-inducible factor-1α on the regulation of brain injury/protection in rats with acute cerebral infarction.
METHODS: Male Sprague-Dawley rats were randomized into three groups: sham operation group (sham), MACO-24 h group, and MACO-72 h group. A middle cerebral artery occlusion (MCAO) model was prepared by thread embolization in the latter two groups. TTC, Nissl staining, immunohistochemical staining and western blot were used to detect infarct volume and microglia morphology in rat brain tissue, the expression levels of hypoxia-inducible factor 1α, caspase 3, interleukin-1β and p-NF-κBp65 were detected, and the secretion levels of interleukin-6 and tumor necrosis factor-α in rat peripheral blood. The study protocol was approved by the Animal Ethics Committee of the First Affiliated Hospital of Jiamusi University (approval No. JMSU-210).
RESULTS AND CONCLUSION: Compared with the sham group, the cerebral infarction area in the MCAO groups was significantly increased, and the brain nerve cells were seriously damaged, arranged disorderly and reduced significantly in number. However, there was no significant difference between the MCAO-24 h group and the MCAO-72 h group. Compared with the sham group, the expression levels of hypoxia-inducible factor 1α, caspase3, p-NF-κBp65, and interleukin-1β in the brain tissue of the MCAO groups were significantly increased (P < 0.05, P < 0.01). The secretion levels of interleukin-6 and tumor necrosis factor-α was significantly increased (P < 0.01) in the peripheral blood. However, compared with the MCAO-24 h group, the expression of caspase 3 in the MCAO-72 h group was significantly decreased, while the secretion of interleukin-6 and tumor necrosis factor-α increased. To conclude, hypoxia-inducible factor 1α participates in the brain injury/protection process after acute cerebral infarction, and the time target is determined as 24-72 hours after MCAO. The determination of the time target can provide a sufficient theoretical basis and therapeutic strategy for determining the optimal use time of clinical hypoxia-inducible factor-1α inhibitors.

Key words: acute cerebral infarction, hypoxia-inducible factyor-1α, brain injury, brain protection, rat, animal model

CLC Number:

Bi Sheng, Sheng Baoying, Han Feng, Jiang Yaojia, Li Congyan, Tian Jiaying. Hypoxia-inducible factor 1 alpha is involved in brain injury/protection in rats with acute cerebral infarction[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(35): 5644-5649.

Figures/Tables 7

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