[1]李伟艺,刘红松,高山瑛,等.基于Notch1/NF-κB信号通路探究补阳还五汤对脑缺血再灌注损伤的拮抗作用及其机制[J].西部中医药,2022,35(11):16-21.[doi:10.12174/j.issn.2096-9600.2022.11.04]
　LI Weiyi,LIU Hongsong,GAO Shanying,et al.Protective Effects of Buyang Huanwu Tang on Cerebral Ischemia-reperfusion Injury Based on Notch1/NF-κB Signaling Pathway and Its Mechanism[J].Western Journal of Traditional Chinese Medicine,2022,35(11):16-21.[doi:10.12174/j.issn.2096-9600.2022.11.04]
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基于Notch1/NF-κB信号通路探究补阳还五汤对脑缺血再灌注损伤的拮抗作用及其机制

《西部中医药》[ISSN:2096-9600/CN:62-1204/R]

卷:
35
期数:
2022年11期
页码:
16-21
栏目:
出版日期:
2022-11-15

文章信息/Info

Title:
Protective Effects of Buyang Huanwu Tang on Cerebral Ischemia-reperfusion Injury Based on Notch1/NF-κB Signaling Pathway and Its Mechanism
作者:
李伟艺, 刘红松, 高山瑛, 苏志强
汉中市人民医院中医康复科，陕西 汉中 723000
Author(s):
LI Weiyi, LIU Hongsong, GAO Shanying, SU Zhiqiang
Department of Traditional Chinese Medicine Rehabilitation, Hanzhong People's Hospital, Hanzhong 723000, China
关键词:
脑缺血再灌注损伤; Notch1/NF-B信号通路; Jagged1; 补阳还五汤
Keywords:
cerebral ischemia-reperfusion injury; Notch1/NF-B signaling pathway; Jagged1
分类号:
R223.1+3
DOI:
10.12174/j.issn.2096-9600.2022.11.04
文献标志码:
A
摘要:
目的探讨补阳还五汤对脑缺血再灌注损伤的保护作用及其机制。 方法将75只SD大鼠随机分为假手术组、模型组、补阳还五汤组、补阳还五汤+Jagged1［神经源性位点缺口同源蛋白1抗体（Notch1）激动剂］组、Jagged1组各15只。除假手术组外，其余各组大鼠采用线栓法制备脑缺血模型，缺血1.5 h后再灌注24 h。连续给药7天后计算大鼠神经功能评分；TTC染色检测脑梗死体积分数；HE染色观察海马神经元损伤情况；酶联免疫吸附试验(Enzyme-linked immunosorbent assay，ELISA)法检测白细胞介素6（interleukin-6，IL-6）、肿瘤坏死因子α（tumor necrosis factor α，TNF-α）、丙二醛（malonaldehyde，MDA）含量和谷胱甘肽过氧化物酶(glutathione peroxidase，GSH-Px)、超氧化物歧化酶（superoxide dismutase，SOD）活性；RT-qPCR法检测半胱氨酸蛋白酶3（Caspase-3）、B淋巴细胞瘤(B-cell lymphoma-2，Bcl-2)、Bcl-2相关X蛋白（Bax）mRNA水平；免疫印记（Western blot）法检测脑组织中Notch1、磷酸化激活核转录因子κB p65（phosphorylated nuclear factor-κB p65，p-NF-κB p65）及发状分裂相关增强子1（hairy division related enhancer,Hes1）蛋白表达。 结果与假手术组比较，模型组大鼠神经功能缺损明显，脑梗死体积增加，海马神经元损伤严重，IL-6、TNF-α、MDA水平升高，GSH-Px、SOD活性降低，Caspase-3、Bcl-2、Bax mRNA表达增加，Notch1、p-NF-κB p65及Hes1蛋白表达增加（P＜0.05）。与模型组比较，补阳还五汤可减轻大鼠神经功能缺损、脑梗死程度和海马神经元损伤，降低海马组织IL-6、TNF-α、MDA水平，提高GSHPx、SOD活性，降低Caspase-3、Bcl-2、Bax mRNA表达和Notch1、p-NF-κB p65及Hes1蛋白表达，而Notch1激动剂Jagged1可拮抗补阳还五汤的治疗效果，加重脑缺血再灌注损伤（P＜0.05）。 结论补阳还五汤能够减轻大鼠脑缺血再灌注损伤，其作用机制可能与抑制Notch1/NF-κB信号通路有关。
Abstract:
ObjectiveTo observe the protective effect of Buyang Huanwu Tang on cerebral ischemia-reperfusion injury and its mechanism. MethodsAll 75 SD rats were randomized into sham operation group, the model group, Buyang Huanwu Tang group, Buyang Huanwu Tang+Jagged1(Notch1 agonist) group, and Jagged1 group, with 15 rats in each group. Except sham operation group, the rats in the remaining groups were prepared into cerebral ischemia models by using middle cerebral artery occlusion, ischemia for 1.5 h, and then reperfusion for 24 h. To calculate neurological function scores of the rats after administration for seven days consecutively; to detect cerebral infarct volume fraction by using TTC staining; to observe hippocampal neuron damage by using HE staining; to detect the contents of IL-6, TNF-α and MDA, and the activity of GSH-Px and SOD by adopting ELISA method; to measure the levels of Caspase-3, Bcl-2 and Bax mRNA by using RT-qPCR method; to detect the expressions of Notch1, p-NF-κB p65 and Hes1 protein in cerebral tissue by applying Western blot method. ResultsCompared with sham operation group, the impairment of neurological function of the rats in the model group was noticeable, the volume of cerebral infarction was increased, and hippocampal neurons were severely damaged, the levels of IL-6, TNF-α and MDA were increased, and the activity of GSH-Px and SOD was reduced, the expressions of Caspase-3, Bcl-2 and Bax mRNA were added, and the expressions of Notch1, p-NF-κB p65 and Hes1 protein were increased (P<0.05). Compared with the model group, Buyang Huanwu Tang could alleviate neurologic impairment, the degrees of cerebral infarction and the damage of hippocampal neurons, lower the levels of IL-6, TNF-α and MDA in hippocampal tissue, raise the activity of GSH-Px and SOD, decrease the expressions of Caspase-3, Bcl-2 and Bax mRNA, as well as the expressions of Notch1, p-NF-κB p65 and Hes1 protein, while, Notch1 agonist Jagged1 could antagonize the therapeutic effect of the decoction, aggravating cerebral ischemia-reperfusion injury (P<0.05). ConclusionBuyang Huanwu Tang could relieve cerebral ischemia-reperfusion injury, and its mechanism might be related to restraining Notch1/NF-κB signaling pathway.

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备注/Memo

备注/Memo:
李伟艺（1978—），男，主治医师。研究方向：心脑血管病。国家自然科学基金（8177052088）。
更新日期/Last Update: 2022-11-15