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贺桂莲,谢刘阳,刘春华,侯帆,朱雯雯,贺宏伟,刘飞.益气定眩饮通过抑制凋亡和促进血管新生改善大鼠脑缺血损伤研究[J].湖南中医药大学学报,2021,41(8):1188-1196[点击复制] |
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益气定眩饮通过抑制凋亡和促进血管新生改善大鼠脑缺血损伤研究 |
贺桂莲,谢刘阳,刘春华,侯帆,朱雯雯,贺宏伟,刘飞 |
(湖南中医药大学, 湖南 长沙 410208;甘肃政法大学, 甘肃 兰州 730070;福建医科大学附属福州市第一医院, 福建 福州 350009) |
摘要: |
目的 从抑制神经元细胞凋亡和促进血管新生角度,探讨益气定眩饮改善大鼠脑缺血损伤的作用机制。方法 97只SPF级健康成年雄性SD大鼠,随机选取20只为假手术组,其余大鼠采用大脑中动脉线栓法制作脑缺血模型。选取造模成功的60只SD大鼠随机分为模型组、丁苯酞组、益气定眩饮组,每组20只,分别予以蒸馏水、丁苯酞胶囊及益气定眩饮灌胃干预。Zea-Longa法检测各组1、3、7、14 d时间点脑缺血大鼠神经功能评分,HE染色观察大鼠脑缺血海马组织形态学变化,TUNEL法检测神经凋亡细胞,免疫组化检测缺血脑组织促红细胞生成素(EPO)、促红细胞生成素受体(EPOR)、血管内皮生长因子(VEGF)、脑源性神经营养因子(BDNF)、酪氨酸激酶B (TrkB)蛋白表达。结果 与假手术组比较,模型组细胞凋亡率增高,EPO、EPOR、VEGF、BDNF、TrkB蛋白表达增加(P<0.05);与模型组相比,丁苯酞组、益气定眩饮组神经功能缺损评分、细胞凋亡率明显降低(P<0.05);EPO、EPOR、VEGF、BDNF、TrkB蛋白表达增加(P<0.05)。结论 益气定眩饮对大鼠脑缺血损伤后的神经功能、局部神经元细胞形态均具有改善作用,以14 d效果更显著,推测其可能与上调EPO、EPOR、VEGF、BDNF、TrkB蛋白表达,促进血管新生,改善脑组织供血供氧,从而保护神经元形态与功能、促进受损神经功能修复有关。 |
关键词: 益气定眩饮 促红细胞生成素 血管内皮生长因子 脑源性神经营养因子 酪氨酸激酶B 细胞凋亡 脑缺血 |
DOI:10.3969/j.issn.1674-070X.2021.08.009 |
投稿时间:2021-02-08 |
基金项目:湖南省自然科学基金项目(2018JJ6107);湖南省中医药科研计划项目(201947);长沙市自然科学基金项目(kq1907138);湖南中医药大学中西医结合学院开放基金项目(2018ZXYJH31)。 |
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Yiqi Dingxuan Yin Improved Cerebral Ischemia Injury in Rats by Inhibiting Apoptosis and Promoting Angiogenesis |
HE Guilian,XIE Liuyang,LIU Chunhua,HOU Fan,ZHU Wenwen,HE Hongwei,LIU Fei |
(Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Gansu University of Political Science and Law, Lanzhou, Gansu 730070, China;Affiliated Fuzhou First Hospital of Fujian Medical University, Fuzhou, Fujian 350009, China) |
Abstract: |
Objective To investigate the mechanism of Yiqi Dingxuan Yin in improving cerebral ischemia injury in rats from the perspective of inhibiting neuronal apoptosis and promoting angiogenesis. Methods 97 SPF healthy adult male SD rats, a total of 20 rats were randomly selected as the sham operation group. The other rats were cerebral ischemia model by middle cerebral artery line embolization. 60 SD rats successfully modeled were randomly divided into model group, butylphthalide group and Yiqi Dingxuan Yin group, with 20 rats in each group. Distilled water, butylphthalide capsule and Yiqi Dingxuan Yin were given for intragastric intervention. Zea-Longa method was used to detect the neurological function scores of rats with cerebral ischemia at 1, 3, 7 and 14 days in each group. HE staining was used to observe the morphological changes in the hippocampus of rats with cerebral ischemia. Nerve apoptosis cells were detected by TUNEL method. The expression levels of erythropoietin (EPO), erythropoietin receptor (EPOR), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), tyrosinine-stimulated B (TrkB) protein in ischemic brain tissue were detected by immunohistochemistry. Results Compared with sham operation group, cell apoptosis rate and protein expression of EPO, EPOR, VEGF, BDNF, TrkB in model group were increased (P<0.05). Compared with model group, nerve function deficit score and cell apoptosis rate were significantly decreased (P<0.05), the protein expression of EPO, EPOR, VEGF, BDNF, TrkB increased (P<0.05) in butylphthalide group and Yiqi Dingxuan Yin group. Conclusion Yiqi Dingxuan Yin can improve the neural function and the morphology of local neurons after cerebral ischemia injury in rats, and with more significant effect of 14 days. It is speculated that it may be related to the up-regulation of EPO, EPOR, VEGF, BDNF, TrkB protein expressionpromoting angiogenesis, improving cerebral blood flow and oxygen supply, thus protecting neurons form and function, promoting restoration of the damaged neural function. |
Key words: Yiqi Dingxuan Yin erythropoietin vascular endothelial growth factor brain-derived neurotrophic factor tyrosinine-stimulated B cell apoptosis cerebral ischemia |
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