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电针对大鼠蛛网膜下腔出血通过抑制 HIF-1α 来增强脑血流灌注。

Electroacupuncture enhances cerebral blood perfusion by inhibiting HIF-1α in rat subarachnoid hemorrhage.

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Department of Rehabilitation, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

出版信息

Brain Res. 2024 Sep 15;1839:149010. doi: 10.1016/j.brainres.2024.149010. Epub 2024 May 17.

Abstract

OBJECTIVE

Cerebral blood perfusion (CBP) reduction is a prevalent complication following subarachnoid hemorrhage (SAH) in clinical practice, often associated with long-term cognitive impairment and prognosis. Electroacupuncture (EA), a widely utilized traditional Chinese therapy for central nervous system disorders, has demonstrated promising therapeutic effects. This study aims to investigate the therapeutic potential of EA in restoring CBP in SAH rats and to explore the mechanisms involving HIF-1α in this process.

METHODS

Rats were randomly assigned to one of five groups, including Sham, SAH, EA, EA + Saline, and EA + dimethyloxallyl glycine (DMOG) groups. EA treatment was administered for 10 min daily, while DMOG were intraperitoneally injected. Behavioral tests, cerebral blood flow monitoring, vascular thickness measurement, western blotting, and immunofluorescence staining were conducted to assess the therapeutic effects of EA on cerebral blood flow.

RESULTS

SAH resulted in elevated levels of HIF-1α, endothelin (ET), ICAM-1, P-SELECTIN, E-SELECTIN, and decreased level of eNOS in the brain. This led to cerebral vasospasm, decreased CBF, and cognitive deficits in the rat SAH model. EA intervention downregulated the expression of HIF-1α, ET, ICAM-1, P-SELECTIN, and E-SELECTIN, while increasing eNOS expression. This alleviated cerebral vasospasm, restored CBF, and improved cognitive function. However, the administration of the HIF-1α stabilizer (DMOG) counteracted the therapeutic effects of EA.

CONCLUSION

EA promotes the recovery of cerebral blood flow after SAH injury, attenuates cerebral vasospasm, and accelerates the recovery of cognitive dysfunction, and its mechanism of action may be related to the inhibition of the HIF-1α signaling pathway.

摘要

目的

脑血流灌注(CBP)减少是临床实践中蛛网膜下腔出血(SAH)的常见并发症,常伴有长期认知障碍和预后不良。电针(EA)是一种广泛应用于中枢神经系统疾病的传统中医疗法,已显示出有希望的治疗效果。本研究旨在探讨 EA 恢复 SAH 大鼠 CBP 的治疗潜力,并探讨该过程中涉及 HIF-1α的机制。

方法

将大鼠随机分为五组,包括假手术组、SAH 组、EA 组、EA+生理盐水组和 EA+二甲基草酰甘氨酸(DMOG)组。EA 治疗每天进行 10 分钟,同时腹腔内注射 DMOG。通过行为测试、脑血流监测、血管厚度测量、Western blot 和免疫荧光染色来评估 EA 对脑血流的治疗效果。

结果

SAH 导致大脑中 HIF-1α、内皮素(ET)、ICAM-1、P-选择素、E-选择素水平升高,eNOS 水平降低,导致大脑血管痉挛、CBF 降低和大鼠 SAH 模型认知功能障碍。EA 干预下调 HIF-1α、ET、ICAM-1、P-选择素和 E-选择素的表达,同时增加 eNOS 的表达。这缓解了脑血管痉挛,恢复了 CBF,并改善了认知功能。然而,HIF-1α稳定剂(DMOG)的给药抵消了 EA 的治疗效果。

结论

EA 促进了 SAH 损伤后脑血流的恢复,减轻了脑血管痉挛,加速了认知功能障碍的恢复,其作用机制可能与抑制 HIF-1α信号通路有关。

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