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丹参注射液通过HIF-1α/CXCR4/NF-κB信号通路抑制神经炎症,减轻脑缺血/再灌注损伤。

Danshen injection mitigated the cerebral ischemia/reperfusion injury by suppressing neuroinflammation via the HIF-1α/CXCR4/NF-κB signaling pathway.

作者信息

Chen Gao, Jin Zhan, Wang Xi, Yu Qi-Hui, Hu Gao-Bo

机构信息

School of Medicine, Quzhou College of Technology.

Urology Department, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, China.

出版信息

Neuroreport. 2024 Jul 1;35(10):601-611. doi: 10.1097/WNR.0000000000002043. Epub 2024 May 20.

Abstract

Danshen injection (DI) is effective in treating cardiovascular and cerebrovascular diseases, including ischemic stroke (IS), including IS, but its mechanism is unclear. A middle cerebral artery occlusion model was used to simulate ischemia/reperfusion (I/R) injury in SD rats. Overexpression of hypoxia-inducible factor 1α (HIF-1α) was achieved by AAV-HIF-1α. Rats were treated with DI or saline. Neurological scores and infarction rates were assessed. I/R damage was examined by HE, 2,3,5-triphenyltetrazolium and Nissl stainings. Expression levels of relative proteins [TNF-α, IL-6, IL-1β, SOD, MDA, ROS, HIF-1α, CXC chemokine receptor 4 (CXCR4) and NF-κB] were measured. DI treatment improved neurological scores and reduced infarction rates, suggesting that it inhibits inflammation and oxidative stress. The expression levels of HIF-1α, CXCR4 and NF-κB were decreased. However, the effectiveness of DI on inflammation inhibition was lost after HIF-1α overexpression. DI may directly target HIF-1α to suppress neuroinflammation and reduce I/R injury by suppressing the HIF-1α/CXCR4/NF-κB signaling pathway.

摘要

丹参注射液(DI)对包括缺血性中风(IS)在内的心脑血管疾病有效,但其机制尚不清楚。采用大脑中动脉闭塞模型模拟SD大鼠的缺血/再灌注(I/R)损伤。通过腺相关病毒-HIF-1α实现缺氧诱导因子1α(HIF-1α)的过表达。大鼠接受DI或生理盐水治疗。评估神经功能评分和梗死率。通过苏木精-伊红染色、2,3,5-三苯基四氮唑染色和尼氏染色检查I/R损伤。检测相关蛋白[肿瘤坏死因子-α、白细胞介素-6、白细胞介素-1β、超氧化物歧化酶、丙二醛、活性氧、HIF-1α、CXC趋化因子受体4(CXCR4)和核因子-κB]的表达水平。DI治疗改善了神经功能评分并降低了梗死率,表明其抑制炎症和氧化应激。HIF-1α、CXCR4和核因子-κB的表达水平降低。然而,HIF-1α过表达后,DI对炎症的抑制作用丧失。DI可能直接靶向HIF-1α,通过抑制HIF-1α/CXCR4/核因子-κB信号通路来抑制神经炎症并减少I/R损伤。

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