川芎嗪预处理脐带间充质干细胞移植治疗缺血性脑卒中的作用机制  

Study on the mechanism of tetramethylpyrazine pretreatment umbilical cord mesenchymal stem cell trans-plantation in the treatment of ischemic stroke

作　　者：曹慧玲[1] 张洁 朱小飞[1] 钱世宁 陈云峰[1] CAO Huiling;ZHANG Jie;ZHU Xiaofei;QIAN Shining;CHEN Yunfeng(Department of Clinical Laboratory,the Affiliated Hospital of Nanjing University of Chinese Medi-cine,Nanjing 210029,Jiangsu,China)

机构地区：[1]南京中医药大学附属医院检验科,江苏南京210029

出　　处：《实用医学杂志》2025年第2期178-185,共8页The Journal of Practical Medicine

基　　金：国家自然科学基金青年项目(编号:81703830)。

摘　　要：目的 将川芎嗪预处理脐带间充质干细胞(ucMSCs)移植入大鼠缺血性脑卒中模型,探讨治疗效果并进一步发掘其作用的机制及关键基因。方法 建立大鼠缺血性脑卒中模型,经尾静脉移植ucMSCs和川芎嗪预处理后的ucMSCs,进行神经功能评分、TTC染色和梗死率计算,观察ucMSCs在脑组织定位情况,采用芯片技术对各实验组进行研究,对样本进行数据标准化处理,生物信息学分析筛选差异基因并进行PCR验证。结果 川芎嗪预处理后的ucMSCs移植效果显著高于未处理组,表现在神经功能评分下降明显,TTC染色显示梗死灶减少和梗死率降低显著,观察发现该组ucMSCs定位于脑损伤组织的数量明显多于未处理组,根据筛选条件,筛出2 905个差异mRNA,其中1 754个上调、1 151个下调,依据倍数变化值≥2.0且P≤0.05,得到27个与趋化因子信号通路相关的差异基因,分析结果显示与细胞迁移密切相关且表达激活的基因有4个,分别为Ccr6、Ccr3、Cxcr1和Ccl6,随机验证结果证实Ccr3及Cxcr1基因表达均显著升高。结论 川芎嗪预处理ucMSCs显著提高了大鼠缺血性脑卒中的治疗效果,预处理后的ucMSCs迁移至脑损伤部位数量明显增加,分析认为可能与川芎嗪激活多种趋化因子Ccr6、Ccr3、Cxcr1和Ccl6的表达密切相关。Objective To investigate the therapeutic effect,underlying mechanism,and key genes involved in tetramethylpyrazine-pretreated umbilical cord mesenchymal stem cell(ucMSC)transplantation in a rat model of ischemic stroke.Methods The rat MCAO model was established,and umbilical cord-derived mesenchymal stem cells(ucMSCs)pretreated with or without tetramethylpyrazine were transplanted via the tail vein.Neurological function scores,TTC staining,and infarct rates were assessed.Localization of ucMSCs in brain tissue was observed.Experimental groups were analyzed using chip technology,and sample data were standardized.Bioinfor‐matics analysis was employed to identify differential genes,which were subsequently validated by PCR.Results The treatment effect in ucMSCs pretreated with tetramethylpyrazine group was significantly superior to that of the untreated group,as evidenced by a significant reduction in neurological function score,infarct rate,and infarct area observed through TTC staining.Moreover,the treated group exhibited a significantly higher number of ucMSCs located within brain injury tissues compared to the untreated group.Subsequently,2905 differential mRNA were screened based on predetermined criteria,including 1754 up-regulated and 1151 down-regulated genes.Among these differentially expressed genes related to the chemokine signaling pathway(identified using a multiple change value≥2.0 and P value≤0.05),we identified 27 genes of interest.Notably,our analysis revealed activation of four genes closely associated with cell migration:Ccr6,Ccr3,Cxcr1 and Ccl6 respectively.Random verification experiments further confirmed a significant increase in gene expression for both Ccr3 and Cxcr1.Conclusions Pretreatment of umbilical cord-derived mesenchymal stem cells(ucMSCs)with tetramethylpyrazine significantly augmented the therapeutic efficacy in a rat model of ischemic stroke.Following pretreatment,there was a substantial increase in the migration of ucMSCs towards the site of brain injury.Our analysis suggests

关 键 词：川芎嗪 脑卒中 脐带间充质干细胞 迁移 趋化因子 

分 类 号：R285.5[医药卫生—中药学]