甲状腺素对动脉瘤性蛛网膜下腔出血大鼠脑缺氧诱导因子-1α表达的影响及其机制*

doi:10.12047/j.cjap.5985.2020.135

中国应用生理学杂志 ›› 2020, Vol. 36 ›› Issue (6): 648-652.doi: 10.12047/j.cjap.5985.2020.135

甲状腺素对动脉瘤性蛛网膜下腔出血大鼠脑缺氧诱导因子-1α表达的影响及其机制^*

冉卉¹, 尹浩², 刘窗溪², 韩国强², 高方友², 谌鸿斌², 付航³, 徐晓钟⁴, 黎涛⁵, 马骏^2△

1.铜仁市人民医院神经外科, 贵州铜仁 554309;
2.贵州省人民医院神经外科, 贵州贵阳 550002;
3.清镇市人民医院神经外科, 贵州贵阳 551400;
4.毕节市中医院神经外科, 贵州贵阳 551700;
5.赣州市人民医院神经外科, 贵州贵阳 341000

收稿日期:2019-12-03 修回日期:2020-07-24 出版日期:2020-11-28 发布日期:2021-03-15
通讯作者: ^△Tel: 13985117823; E-mail: yiyuechujian@163.com

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

RAN Hui¹,YIN Hao², LIU Chuang-xi ², HAN Guo-qiang², GAO Fang-you², SHEN Hong-bin ², FU Hang ³, XU Xiao-zhong⁴, LI Tao⁵, MA Jun ^{2 △}

1. Department of Neurosurgery, Tongren Municipal People's Hospital, Tongren 554309;
2. Department of Neurosurgery, Guizhou Provincial People's Hospital, Guiyang 550002;
3. Department of Neurosurgery, Qingzhen Municipal People's Hospital, Guiyang 551400;
4. Department of Neurosurgery, Bijie Hospital of Traditional Chinese Medicine, Guiyang 551700;
5. Department of Neurosurgery, Ganzhou Municipal People's Hospital, Guiyang 341000, China

Received:2019-12-03 Revised:2020-07-24 Online:2020-11-28 Published:2021-03-15

摘要/Abstract

摘要： 目的:探讨甲状腺素(T4)对动脉瘤性蛛网膜下腔出血后大鼠脑缺氧诱导因子-1α(HIF-1α)表达的调节及其机制。方法:72只雄性成年SD大鼠随机分为以下4组:蛛网膜下腔出血模型组(SAH)(n=18)、蛛网膜下腔出血+甲状腺素组(SAH+T4)(n=18)、蛛网膜下腔出血+溶剂组(SAH+溶剂组)(n=18)、假手术组(n=18)。颈内动脉穿刺法建立蛛网膜下腔出血的模型,术后行颅脑CT平扫,建模后立即开始给药,按3 μg/100 g腹腔注射,每隔24 h一次,连续3 d,SAH+T4组予甲状腺素干预,SAH+溶剂组予等体积溶剂干预,均在建模后72 h处死;各组6只大鼠经多聚甲醛灌注处死后石蜡包埋切片行免疫组化染色检测HIF-1α及p-Akt蛋白、6只用TUNEL法检测凋亡,6只用干湿重法做脑水肿含量检测。结果:建模成功后SAH组及SAH+T4组、SAH+溶剂组大鼠的脑组织肿胀明显,蛛网膜下腔可见暗红色血凝块。SAH组神经行为学评分、脑含水量、凋亡率、HIF-1α蛋白、p-Akt蛋白均较假手术组明显增高(P＜0.05);SAH+T4组神经行为学评分、HIF-1α蛋白、p-Akt蛋白均较SAH组明显增高,其脑含水量、凋亡均较SAH组明显减少(P＜0.05)。结论:使用T4替代治疗可以上调动脉瘤性蛛网膜下腔出血后大鼠脑HIF-1α蛋白表达水平,可能是通过激活三磷酸肌醇激酶／蛋白激酶B(PI3K/Akt)信号通路,使凋亡率减小,最终大鼠行为学得以改善,对大鼠脑产生保护作用。

关键词: 动脉瘤性蛛网膜下腔出血, 甲状腺素, 大鼠, HIF-1α蛋白, p-Akt蛋白, 凋亡

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

中图分类号:

R743-34

冉卉, 尹浩, 刘窗溪, 韩国强, 高方友, 谌鸿斌, 付航, 徐晓钟, 黎涛, 马骏. 甲状腺素对动脉瘤性蛛网膜下腔出血大鼠脑缺氧诱导因子-1α表达的影响及其机制^*[J]. 中国应用生理学杂志, 2020, 36(6): 648-652.

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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甲状腺素对动脉瘤性蛛网膜下腔出血大鼠脑缺氧诱导因子-1α表达的影响及其机制^*

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

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