Effect of thyroxine on the expression of HIF-1α after aneurysmal subarachnoid hemorrhage in rat brain and its mechanism

doi:10.12047/j.cjap.5985.2020.135

Abstract

Abstract: Objective: To investigate the effect of thyroxine (T4) on the expression of hypoxia inducible factor-1α (HIF-1α) in rat brain after aneurysmal subarachnoid hemorrhage (SAH) and its mechanism. Methods: Seventy-two adult male SD rats were randomly divided into the following 4 groups: subarachnoid hemorrhage model group(SAH), subarachnoid hemorrhage model and T4 group (SAH with T4), subarachnoid hemorrhage model with normal saline group (SAH with vehicle), and sham-operation group, 18 rats in each group. The model of subarachnoid hemorrhage group was established by internal carotid artery puncture. CT plain scan was performed after the modeling immediately, T4 was administrated by intraabdominal injection of 3 μg/100 g every 24 hours for 3 days. SAH with T4 group was treated with thyroxine. SAH with vehicle group was treated with equal volume vehicle, all of them were killed 72 hours after modeling. The brain water content was determined to evaluate the brain edema, the apoptosis of cerebral cortex cells was detected by TUNEL method, and HIF-1α protein and p-Akt protein in cerebral cortex were detected by immunohistochemistry in six SD rats of each group. Results: After the modeling, the brain tissues of SAH group, SAH + T4 group and SAH +vehicle group were swollen obviously, and blood clots were observed in subarachnoid space. The neurobehavioral score,the brain water content, apoptosis index, HIF-1α protein and p-Akt protein in SAH group were significantly higher than those in sham-operation group(P＜0.05).The neurobehavioral score,HIF-1α protein and p-Akt protein in SAH with T4 group were significantly higher than those in SAH group, and the brain water content, apoptosis index were significantly lower than those in SAH group (P＜0.05). Conclusion: The expression of HIF-1α protein in the brain of rats after aneurysm subarachnoid hemorrhage can be upregulated by T4 replacement therapy, which may by activating the signal pathway of inositol triphosphate kinase / protein kinase B (PI3K/Akt). Finally, apoptosis index was decreased, the rat behavior was improved and the brain was protected.

Key words: aneurysmal subarachnoid hemorrhage, thyroxine, rat, hypoxia- inducible factor-1α, PI3K/Akt, apoptosi

CLC Number:

R743-34

RAN Hui,YIN Hao, LIU Chuang-xi , HAN Guo-qiang, GAO Fang-you, SHEN Hong-bin , FU Hang , XU Xiao-zhong, LI Tao, MA Jun. Effect of thyroxine on the expression of HIF-1α after aneurysmal subarachnoid hemorrhage in rat brain and its mechanism[J]. CJAP, 2020, 36(6): 648-652.

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