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补阳还五汤通过PI3K/AKT/eNOS轴减轻大鼠蛛网膜下腔出血所致的脑血管痉挛。

BuyangHuanwu Decoction attenuates cerebral vasospasm caused by subarachnoid hemorrhage in rats via PI3K/AKT/eNOS axis.

作者信息

Li Weiping, Wang Ru, Huang Wei, Shen Yanfang, Du Jumei, Tian Ye

机构信息

The College of Life Sciences, Northwest University, Xi'an 710069, Shaanxi, China.

Department of Neurology, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712000, China.

出版信息

Open Life Sci. 2022 Jul 13;17(1):735-743. doi: 10.1515/biol-2022-0071. eCollection 2022.

Abstract

The ancient Chinese remedy BuyangHuanwu Decoction (BHD) is used to treat qi deficit and blood stasis conditions. This work investigated the effect of BHD on cerebral vasospasm (CVS) caused by subarachnoid hemorrhage (SAH). Rats were randomly assigned into four groups: control group, SAH group, SAH + BHD [13 g/(kg day)] group, and SAH + BHD [26 g/(kg day)] group. The Garcia neurological scoring scale was used to assess neurological dysfunction. Hematoxylin and eosin stains were used to determine the extent of vasospasm by measuring the diameter of the basilar artery. Western blot was used to measure the concentrations of phosphoinositide 3-kinase (PI3K), AKT, and phospho-AKT expression levels. RT-PCR was used to determine PI3K and AKT RNA expressions. Immunohistochemistry and enzyme-linked immunosorbent assay were used to measure levels of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO), respectively, in cerebrospinal fluid. BHD treatment ameliorated CVS and mitigated neurological dysfunction after SAH. Furthermore, the findings suggest that NO concentration was increased through the activation of classical PI3K/AKT signaling and the eNOS pathway. Thus, BHD showed multifaceted roles in preventing damage via decreasing vasospasm and improving neurological impairments caused by CVS after SAH.

摘要

中国古代方剂补阳还五汤(BHD)用于治疗气虚血瘀证。本研究探讨了补阳还五汤对蛛网膜下腔出血(SAH)所致脑血管痉挛(CVS)的影响。将大鼠随机分为四组:对照组、SAH组、SAH + BHD [13 g/(kg·天)]组和SAH + BHD [26 g/(kg·天)]组。采用Garcia神经评分量表评估神经功能障碍。苏木精-伊红染色通过测量基底动脉直径来确定血管痉挛程度。蛋白质免疫印迹法用于检测磷酸肌醇3激酶(PI3K)、AKT及磷酸化AKT的表达水平。逆转录-聚合酶链反应用于测定PI3K和AKT的RNA表达。免疫组织化学法和酶联免疫吸附测定法分别用于检测脑脊液中内皮型一氧化氮合酶(eNOS)和一氧化氮(NO)的水平。补阳还五汤治疗可改善SAH后的CVS并减轻神经功能障碍。此外,研究结果表明,通过激活经典的PI3K/AKT信号通路和eNOS途径可使NO浓度升高。因此,补阳还五汤在预防SAH后CVS引起的血管痉挛和改善神经损伤方面具有多方面作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c13/9281585/3528b9e7362f/j_biol-2022-0071-fig001.jpg

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