Protective effects of combination of Xuesaitong and aspirin on cerebral ischemia and reperfusion injury in rats
Article
Figures
Metrics
Preview PDF
Reference
Related
Cited by
Materials
摘要:
目的：探讨血塞通与阿司匹林联合用药对大鼠脑缺血再灌注损伤的保护作用及其作用机制。 方法：将150只雄性SD大鼠随机分为假手术组、大脑中动脉缺血再灌注（MCAO/R）模型组、血塞通组、阿司匹林组、血塞通+阿司匹林组。预给药7天，末次给药1h后制作MCAO/R模型。按照Longa的5级评分方法进行神经功能缺损评分；通过测量脑含水量观察脑水肿；TTC染色测定脑梗死体积。采用试剂盒测定血清、大脑皮层和海马组织中MDA的含量，SOD、CAT和GSH-Px的活性；ELISA检测IL-1β、IL-4、IL-6、IL-10、TNF-α、MCP-1的水平；Western blot 测定分析大脑皮层组织中Nrf2、HO-1、IκBα、NF-κB/p65蛋白的表达情况。 结果：血塞通组、阿司匹林组、血塞通与阿司匹林合用组均能显著改善MCAO/R大鼠神经功能缺损，减轻脑水肿，减少脑梗死体积，降低血清、大脑皮层和海马组织中的犬尿素、MDA、MCP-1、TNF-α、IL-1β和IL-6水平，降低MDA含量，增加SOD、CAT、GSH-Px、IL-4和IL-10水平。此外，血塞通与阿司匹林单用及合用均能降低NF-κB/p65在细胞核内的表达，同时增加IκBα，HO-1和细胞核内Nrf2的表达。且血塞通与阿司匹林联合用药对CIRI大鼠的保护作用效果优于二者单用。 结论：血塞通与阿司匹林联合用药能明显抑制MCAO/R大鼠血清，大脑皮层和海马的氧化应激和炎症反应，且血塞通与阿司匹林合用的作用效果优于二者单用。血塞通与阿司匹林联合用药对大鼠脑缺血再灌注损伤具有协同治疗作用，值得进一步临床研究。
Abstract:
Objective To investigate the protective effects of the combination of Xuesaitong (XST) and aspirin on cerebral ischemia and reperfusion injury (CIRI) in rats, and further explore the underlying mechanisms. Methods A total of 150 male Sprague-Dawley (SD) rats were randomly divided into five groups with 30 rats in each group: sham group, middle cerebral artery occlusion/reperfusion (MCAO/R) model group, XST group, aspirin group, and XST + aspirin group. Rats were pretreated with XST, aspirin, or XST + aspirin for 7 d. One hour after the last administration, a model of CIRI was induced by MCAO/R. Neurological deficits were assessed using Longa’s five-point scale. Cerebral edema was detected by the measurement of brain water content. The volume of cerebral infarction was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), as well as levels of malonaldehyde (MDA) were detected by commercial kits. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of interleukin-1 (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1), and kynurenine in serum, cerebral cortex, and hippocampus of MCAO/R rats. The protein expression of nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (HO-1), I-kappa B alpha (IκBα), and nuclear factor kappa B (NF-κB)/p65 in the cortex were analyzed by western blotting. Results Treatment of XST, aspirin, and XST + aspirin significantly alleviated the neurological deficits, cerebral edema, and cerebral infarct volume induced by MCAO/R. Treatment of XST, aspirin, and XST + aspirin also reduced MDA, IL-1β, IL-6,TNF-α, MCP-1, and kynurenine levels, and increased SOD, CAT, GSH-Px, IL-4, and IL-10 levels in serum, cerebral cortex, and hippocampus of MCAO/R rats. Furthermore, treatment of XST, aspirin, and XST + aspirin decreased the expression of nuclear NF-κB/p65 and increased the expression of IκBα, nuclear Nrf2, and HO-1. Importantly, the combination of XST and aspirin enhanced the protective effects of XST or aspirin treatment alone on CIRI in rats. Conclusion The combination of XST and aspirin significantly inhibited oxidative stress and inflammation in serum, cerebral cortex, and hippocampus of MCAO/R rats. The combination of XST and aspirin exerted more protective effects than XST or aspirin treatment alone. The combination of XST and aspirin might provide the synergistic therapeutic effects on CIRI, and deserve further clinical investigation.
关键词:
血塞通;阿司匹林;脑缺血再灌注损伤;氧化应激;炎症反应
Keywords:
Project Supported:
This work is supported by the Major collaborative innovation projects of Chinese Academy of Medical Sciences (No. CAMS-2016-I2M-1-010，2016-I2M-1-012).
Na-na Zhao, Shi-min Tang, Xin-yue Li, Yong-mei Wu, Yu-ting Zhou, Jin-feng Shen, Song Fang, Xiang-bao Meng, Gui-bo Sun, Xiao-bo Sun. Protective effects of combination of Xuesaitong and aspirin on cerebral ischemia and reperfusion injury in rats[J]. Chinese Herbal Medicines (CHM),2018,10(2):222-229
