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血栓通注射液(冻干)联合丹参冻干注射液通过减轻氧化应激对大鼠局灶性脑缺血/再灌注损伤的保护作用。

Xueshuantong injection (lyophilized) combined with salvianolate lyophilized injection protects against focal cerebral ischemia/reperfusion injury in rats through attenuation of oxidative stress.

机构信息

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.

Key Laboratory of Formula of Traditional Chinese Medicine (Tianjin University of Traditional Chinese Medicine), Ministry of Education, Tianjin 300193, China.

出版信息

Acta Pharmacol Sin. 2018 Jun;39(6):998-1011. doi: 10.1038/aps.2017.128. Epub 2017 Oct 12.

Abstract

Salvianolate lyophilized injection (SLI) and Xueshuantong injection (lyophilized) (XST) are two herbal standardized preparations that have been widely used in China for the treatment of acute cerebral infarction. In this study, we investigated the neuroprotective effects of SLI combined with XST in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). Wistar rats were subjected to 1.5 h of MCAO followed by reperfusion for 3 h, then were treated with SLI or XST alone, or with their combinations via tail vein injection daily for 3 d. Edaravone (EDI, 6 mg·kg·d) was used as a positive control drug, We showed that administration of a combination of 1X1S (XST 100 mg·kg·d plus SLI 21 mg·kg·d) more effectively protected the ischemic brains than SLI or XST used alone. Administration of 1X1S not only significantly decreased neurological deficit scores and infarct volumes and increased regional cerebral blood flow, but also inhibited the activation of both microglia and astrocytes in the hippocampus. Furthermore, administration of 1X1S significantly decreased the levels of MDA and ROS with concomitant increases in the levels of antioxidant activity (SOD, CAT and GSH) in the brain tissues as compared with SLI and XST used alone. Moreover, administration of 1X1S remarkably upregulated the expression of Nrf-2, HO-1 and NQO-1, and downregulated the expression of Keap1 and facilitated the nuclear translocation of Nrf-2 in the brain tissues as compared with XST used alone. Our study demonstrates that a combination of 1X1S effectively protects MCAO/R injury via suppressing oxidative stress and the Nrf-2/Keap1 pathway.

摘要

丹酚酸 B 冻干注射液(SLI)和丹参冻干注射液(XST)是两种在中国广泛用于治疗急性脑梗死的草药标准化制剂。在这项研究中,我们研究了 SLI 联合 XST 在大脑中动脉闭塞再灌注(MCAO/R)大鼠模型中的神经保护作用。Wistar 大鼠接受 1.5 h 的 MCAO 后再灌注 3 h,然后通过尾静脉注射单独或联合 SLI 和 XST 治疗 3 d。依达拉奉(EDI,6 mg·kg·d)作为阳性对照药物。我们发现,1X1S(XST 100 mg·kg·d 加 SLI 21 mg·kg·d)联合给药比单独使用 SLI 或 XST 更有效地保护缺血性大脑。1X1S 给药不仅显著降低神经功能缺损评分和梗死体积,增加局部脑血流,还抑制海马中小胶质细胞和星形胶质细胞的激活。此外,与单独使用 SLI 和 XST 相比,1X1S 给药显著降低了脑组织中 MDA 和 ROS 的水平,同时增加了抗氧化活性(SOD、CAT 和 GSH)的水平。此外,与单独使用 XST 相比,1X1S 给药显著上调了 Nrf-2、HO-1 和 NQO-1 的表达,下调了 Keap1 的表达,并促进了 Nrf-2 在脑组织中的核转位。我们的研究表明,1X1S 联合治疗通过抑制氧化应激和 Nrf-2/Keap1 通路有效保护 MCAO/R 损伤。

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