文章摘要
欧阳海艳,陈偶英,张慧萍,张长应,单 辉,吴石星.小檗碱对缺血性脑梗死大鼠氧化应激/炎症反应、血管生成的作用研究[J].,2022,(23):4417-4422
小檗碱对缺血性脑梗死大鼠氧化应激/炎症反应、血管生成的作用研究
Effect of Berberine on Oxidative Stress/Inflammatory Response and Angiogenesis in Rats with Ischemic Cerebral Infarction
投稿时间:2022-03-23  修订日期:2022-04-18
DOI:10.13241/j.cnki.pmb.2022.23.004
中文关键词: 小檗碱  缺血性脑梗死  大鼠  氧化应激  炎症反应  血管生成
英文关键词: Berberine  Ischemic cerebral infarction  Rat  Oxidative stress  Inflammatory response  Angiogenesis
基金项目:湖南省卫生健康委科研计划项目(20200919)
作者单位E-mail
欧阳海艳 湖南中医药大学 湖南 长沙 410208 oyhy2022@163.com 
陈偶英 湖南中医药大学 湖南 长沙 410208  
张慧萍 湖南省脑科医院神经内科 湖南 长沙 410007  
张长应 湖南省脑科医院神经内科 湖南 长沙 410007  
单 辉 湖南省财贸医院麻醉手术科 湖南 长沙 410011  
吴石星 湖南省脑科医院神经内科 湖南 长沙 410007  
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中文摘要:
      摘要 目的:探讨小檗碱对缺血性脑梗死大鼠氧化应激/炎症反应、血管生成的作用。方法:选取60只SPF级SD大鼠,随机分为对照组、模型组和小檗碱组各20只。建立大鼠脑缺血再灌注损伤模型。术后及给药后7d采用Longa标准评分评估大鼠神经功能。检测各组大鼠脑组织的抗氧化活性和炎症因子水平。采用免疫组化检测脑缺血再灌注皮质微血管密度(MVD)。采用实时定量聚合酶链反应(qRT-PCR)检测低氧诱导生长因子- 1 (HIF-1 )和血管内皮生长因子(VEGF) mRNA表达水平。采用蛋白免疫印迹试验检测VEGF和HIF-1 蛋白表达水平。结果:模型组和小檗碱组大鼠术后具有神经功能缺损症状表现,Longa评分均高于对照组。给药7 d后,模型组和小檗碱组大鼠Longa评分均高于对照组(P<0.05),且小檗碱组大鼠Longa评分低于模型组(P<0.05)。与对照组比较,模型组丙二醛(MDA)水平显著升高,而谷胱甘肽过氧化物酶(GSH-Px)和超氧化物岐化酶(SOD)活性显著降低(P<0.05)。与模型组比较,小檗碱组MDA水平显著降低,而GSH-Px和SOD活性显著升高(P<0.05)。与对照组比较,模型组白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平显著升高(P<0.05)。与模型组比较,小檗碱组IL-1β、TNF-α水平显著降低,差异有统计学意义(P<0.05)。给药7 d后,模型组和小檗碱组MVD、VEGF mRNA和HIF-1 mRNA表达水平均高于对照组(P<0.05),而小檗碱组MVD、VEGF mRNA和HIF-1 mRNA表达水平高于模型组(P<0.05)。给药7 d后,小檗碱组和模型组VEGF和HIF-1 蛋白表达水平均高于对照组(P<0.05),而小檗碱组VEGF和HIF-1 蛋白表达水平高于模型组(P<0.05)。结论:小檗碱通过抑制氧化应激/炎症反应、促进血管生成从而达到脑保护作用,其机制可能与激活HIF-1 /VEGF信号通路有关。
英文摘要:
      ABSTRACT Objective: To investigate the effect of berberine on oxidative stress/inflammation and angiogenesis in rats with ischemic cerebral infarction. Methods: Sixty SPF SD rats were randomly divided into control group, model group and berberine group with 20 rats each. To establish cerebral ischemia-reperfusion injury model in rats.The neurological function of rats was evaluated by Longa standard score after surgery and 7 d after administration.The levels of antioxidant activity and inflammatory factors in brain tissues of rats in each group were detected.Cortical microvascular density (MVD) was detected by immunohistochemistry. The mRNA expression levels of hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) were detected by real-time quantitative polymerase chain reaction (QRT-PCR). The protein expression levels of VEGF and HIF-1 were detected by western blot assay. Results: The rats in the model group and the berberine group had postoperative neurological deficit symptoms, and the Longa score was higher than that in the control group (P<0.05). After 7 days of administration, the Longa scores of the rats in the model group and the berberine group were higher than those in the control group (P<0.05), and the Longa scores of the rats in the berberine group were lower than those in the model group (P<0.05). Compared with control group,malondialdehyde(MDA) level in model group was significantly increased,while glutathioneperoxidase(GSH-Px) and superoxidedismutase(SOD) activities were significantly decreased (P<0.05). Compared with model group, the level of MDA in berberine group was significantly decreased, while the activities of GSH-Px and SOD were significantly increased(P<0.05). Compared with control group, the levels of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in model group were significantly increased(P<0.05). Compared with model group, the levels of IL-1β and TNF-α in berberine group were significantly decreased(P<0.05). After 7 days of administration, the expression levels of MVD, VEGF mRNA and HIF-1 mRNA in berberine group and model group were higher than those in control group(P<0.05), and the expression levels of MVD, VEGF mRNA and HIF-1 mRNA in berberine group were significantly higher than those in model group(P<0.05). After 7 days of administration, the expression levels of VEGF and HIF-1 protein in berberine group and model group were higher than those in control group(P<0.05), and the expression levels of VEGF and HIF-1 protein in berberine group were significantly higher than that in model group(P<0.05). Conclusion: Berberine inhibits oxidative stress/inflammation and promotes angiogenesis to achieve brain protection, which may be related to the activation of HIF-1 /VEGF signaling pathway.
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