川芎嗪对脐带间充质干细胞移植缺血性脑卒中迁移率的影响及作用机制  

Effect and mechanism of Tetramethylpyrazine on the migration of umbilical cord mesenchymal stem cell in the treatment of ischemic stroke

作　　者：曹慧玲[1] 汪小蓉[1] 朱小飞[1] 张洁 钱世宁 CAO Huiling;WANG Xiaorong;ZHU Xiaofei;ZHANG Jie;QIAN Shining(Department of Clinical Laboratory,the Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China;不详)

机构地区：[1]南京中医药大学附属医院检验科,南京210029

出　　处：《实用医学杂志》2022年第6期726-730,737,共6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 观察体内外川芎嗪(TMP)对脐带间充质干细胞(ucMSCs)迁移的影响并研究其相关作用机制。方法 体内尾静脉移植ucMSCs入脑中动脉栓塞模型(MCAO)大鼠,荧光显微镜观察GFP-ucMSCs的迁移定位情况,Western blot检测基质细胞衍生因子-1(SDF-1)及其受体CXCR4的表达;体外采用Transwell法检测ucMSCs的迁移,观察TMP处理以及加入拮抗剂后对ucMSCs迁移率的影响,ELISA检测白介素-1β(IL-1β)的表达水平,检测迁移相关蛋白表达。结果 体内结果发现TMP预处理后ucMSCs迁移至脑梗死区的数量(IOD 2.9×105)较未处理组(IOD 0.4×105)显著增加(P <0.05),SDF-1和CXCR4的表达量也显著升高(P <0.05),且加入拮抗剂后各指标均明显降低(P <0.05);体外实验显示TMP预处理后的ucMSCs迁移细胞数由每区域20个提高至88个(P <0.05),与CXCR4的表达升高一致;TMP处理损伤PC12细胞可有效降低炎症因子IL-1β的表达(17.2 pg/mL降至13.5 pg/mL)。结论 川芎嗪通过调节SDF-1/CXCR4轴提高脐带间充质干细胞移植迁移率,并抑制炎症反应改善移植微环境,为中医药与干细胞联合治疗缺血性脑卒中提供实验依据。Objective To observe the effect of tetramethylpyrazine(TMP)on the migration of umbilical cord mesenchymal stem cells(ucMSCs)and investigate the mechanism in vivo and vitro separately.Methods In vivo,ucMSCs were transplanted into MCAO rats by tail vein injection.The migration and localization of GFP-ucMSCs were observed by fluorescence microscope.The expression of related proteins SDF-1 and CXCR4 were detected by Western blot.In vitro,the migration of ucMSCs was detected by Transwell method.The effects of TMP treatment and antagonist on the mobility of ucMSCs were observed.The level of interleukin-1β(IL-1β)was detected by ELISA and the expression of migration related proteins was detected.Results In vivo,it was found that the number of ucMSCs migrated and located in the cerebral infarction area after TMP pretreatment(IOD 2.9×105)increased significantly compared to untreated group(IOD 0.4×105)(P<0.05).The expression of SDF-1 and CXCR4 also increased significantly,which was inhibited by adding antagonists(P<0.05);In vitro,the number of migrating cells increased from 20 to 88 per region by TMP pretreatment(P<0.05),which was consistent with the increased expression of CXCR4.The expression of inflammatory factor IL-1βin PC12 cells was reduced by TMP treatment(from 17.2 to 13.5 pg/mL).ConclusionTetramethylpyrazine improves the migration rate of umbilical cord mesenchymal stem cells by regulating SDF-1/CXCR4 axis.The transplantation microenvironment was also improved by inhibiting inflammation.This study provides experimental basis for the combination of traditional Chinese medicine and stem cells in the treatment of ischemic stroke.

关 键 词：川芎嗪 脐带间充质干细胞 脑卒中 移植 迁移 

分 类 号：R285.5[医药卫生—中药学]