摘要
该文旨在研究川芎嗪(tetramethylpyrazine,TMP)联合神经干细胞(neural stem cells,NSCs)移植对大脑中动脉阻塞(middle cerebral artery occlusion,MCAO)模型大鼠的干预作用,并基于干细胞生物学行为调控探讨TMP联合NSCs移植对缺血性脑卒中的作用机制。将MCAO大鼠按神经功能评分随机分为模型组、TMP组、神经干细胞移植(NSCs)组和TMP联合神经干细胞移植(TMP+NSCs)组,同时设立假手术组。以神经功能评分来评价TMP联合NSCs移植对MCAO大鼠神经功能的改善情况;分别以BrdU、BrdU/DCX、BrdU/NeuN和BrdU/GFAP免疫荧光标记法评价NSCs的增殖、迁移、分化情况;蛋白免疫印迹检测基质细胞衍生因子1(SDF-1)、趋化因子C-X-C-基元受体4(CXCR4)的蛋白表达及氧化应激通路核因子E2相关因子2(Nrf2)、胞浆蛋白伴侣分子1(KEAP1)、血红素加氧酶1(HO-1)、醌氧化还原酶1(NQO1)的蛋白表达,研究TMP联合NSCs发生迁移的作用机制。结果发现,TMP联合NSCs移植可以显著改善MCAO大鼠神经功能评分;免疫荧光染色结果显示TMP组、NSCs组、TMP+NSCs组的BrdU^(+)、BrdU^(+)/DCX^(+)、BrdU^(+)/NeuN^(+)、BrdU^(+)/GFAP^(+)细胞数均明显升高,且以联合治疗组最明显;进一步的蛋白免疫印迹结果分析发现TMP组、NSCs组、TMP+NSCs组的CXCR4蛋白表达均显著升高,Nrf2、HO-1、NQO1的蛋白表达上调,KEAP1蛋白表达降低。该研究表明TMP以及NSCs移植均可促进NSCs增殖、迁移和分化,进而促进神经功能恢复,两者联合作用更佳,其作用机制可能与激活Nrf2/HO-1/CXCR4通路有关。
This study aimed to investigate the intervention effect of tetramethylpyrazine(TMP)combined with transplantation of neural stem cells(NSCs)on middle cerebral artery occlusion(MCAO)rat model and to explore the mechanism of TMP combined with NSCs transplantation on ischemic stroke based on the regulation of stem cell biological behavior.MCAO rats were randomly divided into a model group,a TMP group,an NSCs transplantation group,and a TMP combined with NSCs transplantation group according to neu-rological function scores.A sham group was set up at the same time.The neurological function score was used to evaluate the improve-ment of neurological function in MCAO rats after TMP combined with NSCs transplantation.The proliferation,migration,and differen-tiation of NSCs were evaluated by BrdU,BrdU/DCX,BrdU/NeuN,and BrdU/GFAP immunofluorescence labeling.The protein ex-pression of stromal cell-derived factor 1(SDF-1),C-X-C motif chemokine receptor 4(CXCR4),as well as oxidative stress pathway proteins nuclear factor erythroid 2-related factor 2(Nrf2),Kelch-like ECH-associated protein 1(KEAP1),heme oxygenase 1(HO-1),NAD(P)H quinone oxidoreductase 1(NQO1)was detected by Western blot to study the migration mechanism of TMP combined with NSCs.The results showed that TMP combined with NSCs transplantation significantly improved the neurological function score in MCAO rats.Immunofluorescence staining showed a significant increase in the number of BrdU^(+),BrdU^(+)/DCX^(+),BrdU^(+)/NeuN^(+),and BrdU^(+)/CFAP^(+)cells in the TMP,NSCs transplantation,and combined treatment groups,with the combined treatment group showing the most significant increase.Further Western blot analysis revealed significantly elevated expression of CXCR4 protein in the TMP,NSCs transplantation,and combined treatment groups,along with up-regulated protein expression of Nrf2,HO-1,and NQO1,and decreased KEAP1 protein expression.This study showed that both TMP and NSCs transplantation can promote the recovery of neurological function by promoting the prolife
作者
戚明珠
王艳秋
王栋
李卓航
黄荷兰
林娜
苏晓慧
孔祥英
QI Ming-zhu;WANG Yan-qiu;WANG Dong;LI Zhuo-hang;HUANG He-an;LIN Na;SU Xiao-hui;KONG Xiang-ying(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2024年第9期2316-2325,共10页
China Journal of Chinese Materia Medica
基金
国家自然科学基金面上项目(82074048,81673630)
北京市自然科学基金面上项目(7222291)。
关键词
川芎嗪
神经干细胞移植
氧化应激
迁移
tetramethylpyrazine
neural stem cell transplantation
oxidative stress
migration
