[1]张乐国,朱翠敏,夏瑞雪,等.汉黄芩素调节Notch信号通路对脑缺血/再灌注模型小鼠神经细胞凋亡的影响[J].卒中与神经疾病杂志,2024,(01):8-13.[doi:10.3969/j.issn.1007-0478.2024.01.002]
　Zhang Leguo*,Zhu Cuimin,Xia Ruixue*,et al.Impact of wogonin on neuronal apoptosis in a cerebral ischemia/reperfusion mouse model by regulating Notch signaling pathway[J].Stroke and Nervous Diseases,2024,(01):8-13.[doi:10.3969/j.issn.1007-0478.2024.01.002]
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汉黄芩素调节Notch信号通路对脑缺血/再灌注模型小鼠神经细胞凋亡的影响()
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《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
期数:
2024年01期
页码:
8-13
栏目:
论著
出版日期:
2024-02-20

文章信息/Info

Title:
Impact of wogonin on neuronal apoptosis in a cerebral ischemia/reperfusion mouse model by regulating Notch signaling pathway
文章编号:
1007-0478(2024)01-0008-06
作者:
张乐国; 朱翠敏; 夏瑞雪; 贾建普; 张丽冉; 赵泽宇; 霍虹达; 齐曼曼
061001 河北省沧州市中心医院神经内科（张乐国 夏瑞雪 贾建普 张丽冉 赵泽宇），宣传策划科 （朱翠敏），门诊部（霍虹达），麻醉科（齐曼曼）
Author(s):
Zhang Leguo*;  Zhu Cuimin;  Xia Ruixue*;  et al.
*Department of Neurology, Cangzhou Central Hospital, Cangzhou 061001
关键词:
汉黄芩素; Notch信号通路; 脑缺血/再灌注; 神经细胞; 凋亡
Keywords:
Wogonin Notch signaling pathway Cerebral ischemia/reperfusion Neural cells Apoptosis
分类号:
R743.3
DOI:
10.3969/j.issn.1007-0478.2024.01.002
文献标志码:
A
摘要:
目的 探讨汉黄芩素（Wogonin，WOG）通过调节Notch信号通路对脑缺血/再灌注模型（Ischemia/reperfusion，I/R）小鼠神经细胞凋亡的影响。 方法 采用改良线栓堵塞法建立I/R小鼠模型，建模成功后将小鼠随机分为假手术组（Sham组）、模型组（I/R组）、汉黄芩素低、中、高剂量组（WOG-L组、WOG-M组、WOG-H组），汉黄芩素高剂量+Notch信号通路抑制剂组［WOG+3,5-二氟苯乙酰基）-L-丙氨酰基-L-2-苯基甘氨酸叔丁酯（DAPT）组］，每组各15只；采用神经功能缺损评分评价小鼠神经功能损伤，苏木素-伊红（Hematoxylin and eosin，HE）染色法、原位末端标记法（TDT mediated dutp nick end labeling，Tunel）观察小鼠脑组织海马CA1区病理情况及神经细胞凋亡情况，2,3,5-氯化三苯基四氮唑（2,3,5-Triphenyltetrazolium chloride，TTC）染色法计算小鼠脑梗死体积，酶联免疫吸附测定法（Enzyme-linked immunosorbent assay，ELISA）法检测海马组织中肿瘤坏死因子-α（Tumor necrosis factor-α，TNF-α）、白细胞介素-6（Interleukin 6，IL-6）水平，Western blot法检测半胱氨酸蛋白酶-3（Cysteinyl aspartate specific proteinase-3，Caspase-3）及Notch信号通路相关蛋白（受体Notch1、配体蛋白Jagged1、下游转录因子Hes1）表达水平。 结果 与Sham组比较，I/R组小鼠脑组织细胞损伤严重，神经功能缺损评分、脑梗死体积、神经细胞凋亡率、TNF-α及IL-6，Caspase-3，Notch1，Jagged1，Hes1蛋白表达水平显著升高（P>0.05）；与I/R组比较，WOG-L组、WOG-M组、WOG-H组小鼠脑组织细胞损伤减轻，神经功能缺损评分、脑梗死体积、神经细胞凋亡率、TNF-α及IL-6，Caspase-3蛋白表达水平显著降低，Notch1，Jagged1，Hes1表达水平显著升高（P＜0.05）；与WOG-H组比较，WOG+DAPT组DAPT可部分逆转汉黄芩素对I/R组小鼠神经细胞的保护作用（P＜0.05）。 结论 汉黄芩素可以减少脑缺血/再灌注小鼠神经细胞的凋亡，改善神经功能损伤，其作用机制可能与激活Notch信号通路有关。
Abstract:
Objective〖WTBZ〗 To investigate the impact of wogonin (WOG) on neuronal apoptosis in cerebral ischemia/reperfusion (I/R) mice by regulating Notch signaling pathway. 〖WTHZ〗Methods 〖WTBZ〗 The I/R rat model was established by the modified thread plug method. After successful modeling, the mice were randomly grouped into Sham surgery group (Sham group), model group (I/R group), low, medium and high dose Wogonin groups (WOG-L group, WOG-M group, WOG-H group), and high dose Wogonin+Notch signaling pathway inhibitor group (WOG+DAPT group), with 15 mice in each group. The neurological deficit score was applied to evaluate neurological impairment in mice. Hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (Tunel) staining were applied to observe the pathological changes and neuronal apoptosis in the CA1 region of the hippocampus in mice. The 2,3,5-triphenyltetrazolium chloride (TTC) staining method was applied to calculate the volume of cerebral infarction in mice. Enzyme-linked immunosorbent assay (ELISA) was applied to detect the levels of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in the hippocampus. Western blot method was applied to detect the expression of cysteinyl aspartate specific proteinase-3 (Caspase-3) and Notch signaling pathway related proteins (receptor Notch1, ligand protein Jagged1, downstream transcription factor Hes1). 〖WTHZ〗Results 〖WTBZ〗 Compared with the Sham group, the cells of the I/R group mice were severely damaged. The neurological deficit score, cerebral infarction volume, neuronal apoptosis rate, TNF-α and IL-6 levels, Caspase-3, Notch1, Jagged1, and Hes1 protein expression were obviously increased (P>0.05). Compared with the I/R group, the damage of cells in the WOG-L, WOG-M, and WOG-H groups was alleviated. And the neurological deficit score, cerebral infarction volume, neuronal apoptosis rate, TNF-α and IL-6 levels, and Caspase-3 protein expression were obviously reduced, while the expressions of Notch1, Jagged1, and Hes1 were obviously increased (P＜0.05). Compared with the WOG-H group, the experimental results in the WOG+DAPT group showed that DAPT could partially reverse the protective effect of Wogonin on neural cells in the I/R group (P＜0.05). 〖WTHZ〗Conclusion 〖WTBZ〗 Wogonin can reduce the neuronal apoptosis and improve the neurological damage in mice with cerebral ischemia/reperfusion, and its mechanism may be related to the activation of Notch signaling pathway.

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备注/Memo

备注/Memo:
基金项目：河北省医学科学研究课题计划（编号为20220371）
更新日期/Last Update: 2024-02-20