基于甘露糖结合凝集素探讨川芎嗪对脑缺血/缺氧后神经炎症的影响  

Effect of tetramethylpyrazine on neuroinflammation after cerebral ischemia and hypoxia based on mannose-binding lectin

作　　者：段彦哲 孙宇康 滑键林 温春丽 田昊[1] 杨依 楼秀 马存根 闫玉清 宋丽娟 DUAN Yan-zhe;SUN Yu-kang;HUA Jian-lin;WEN Chun-li;TIAN Hao;YANG Yi;LOU Xiu;MA Cun-gen;YAN Yu-qing;SONG Li-juan(Key Laboratory of Multiple Sclerosis and Neurobiology Research Center,National Administration of Traditional Chinese Medicine,Shanxi University of Traditional Chinese Medicine,Jinzhong Shanxi 030619,China;Dept of Neurology,Institute of Brain Science/the First Affiliated Hospital of Shanxi Datong University,Datong Shanxi 037009,China;Key Laboratory of Cell Physiology,Shanxi Medical University,Taiyuan 030001,China;Dept of Traditional Chinese Medicine,Shanxi Provincial People's Hospital,Taiyuan 030001,China)

机构地区：[1]山西中医药大学国家中医药管理局多发性硬化益气活血重点研究室/神经生物学研究中心,山西晋中030619 [2]山西大同大学脑科学研究所/附属第一医院神经科,山西大同037009 [3]山西医科大学细胞生理学省部共建教育部重点实验室,山西太原030001 [4]山西省人民医院中医科,山西太原030001

出　　处：《中国药理学通报》2025年第4期668-676,共9页Chinese Pharmacological Bulletin

基　　金：中国博士后科学基金面上资助项目(No.2020M680912);山西省科技合作交流专项资助项目(No.202304041101004);山西中医药大学科技创新能力培育计划国家自然科学基金培育专项资助项目(No.2024PY-NS-012);山西省研究生创新实践类项目(No.2024KY663)。

摘　　要：目的探究川芎嗪(tetramethylpyrazine,TMP)通过甘露糖结合凝集素(mannose-binding lectin,MBL)对脑缺血/缺氧后神经炎症的影响。方法纳入在山西省人民医院诊断为缺血性脑卒中的患者,在经患者及家属同意后,收集其临床病理资料以及血液和尿液。利用患者的生物样本,通过蛋白组学分析筛选差异蛋白和靶点,并用动物实验验证。小鼠分为sham组、dMCAO组、TMP低、中、高剂量(10、20、40mg·kg^(-1))组,在给药7 d后取材。同时采用mNSS法评估神经功能;TTC染色检测脑梗死体积;行为学评测运动功能;ELISA法检测MASP1、sC5b-9、TNF-α、IL-6和IL-1β;Western blot测定MBL2、MASP2、C3等相关蛋白表达。结果与sham组相比,dMCAO组神经功能损伤加重,给予TMP能明显改善神经功能。dMCAO组中MBL2、C3和MASP2表达升高,TMP治疗后降低。dMCAO组炎症因子IL-1β、IL-6和TNF-α表达升高,TMP抑制了这些炎性因子的表达。结论TMP通过调节MBL抑制缺血/缺氧后的炎性反应,从而减轻脑损伤。Aim To investigate the effect of tetramethylpyrazine(TMP)on neuroinflammation after cerebral ischemia and hypoxia via mannose-binding lectin(MBL).Methods Patients diagnosed with ischaemic stroke at Shanxi Provincial People’s Hospital were included in the study,and their clinicopathological data,as well as blood and urine samples,were collected with the consent of the patients and their families.Using these biological samples,differential proteins and targets were identified by proteomic analysis and subsequently verified with animal experiments.The mice were divided into the sham,dMCAO,and TMP(10,20,40 mg·kg^(-1))treatment groups.After seven days of drug administration,the modified neurological severity score(mNSS)was used to assess the neurological function.TTC staining was used to detect the volume of cerebral infarction.Motor function was evaluated behaviourally,and ELISA was used to detect MASP1,sC5b-9,TNF-α,IL-6,and IL-1β.Western blot was used to determine the expression of relevant proteins,such as MBL2,MASP2,and C3.Results Compared with the sham group,the dMCAO group exhibited increased neurological impairment,which was significantly ameliorated by TMP treatment.The expression levels of MBL2,C3 and MASP2 were elevated in the dMCAO group and were reduced following TMP treatment.Additionally,the dMCAO group showed elevated expression of inflammatory factors IL-1β,IL-6 and TNF-α,which were then suppressed by TMP treatment.Conclusion TMP inhibits the inflammatory response after ischemia and hypoxia by regulating MBL,thus attenuating brain injury.

关 键 词：缺血性脑卒中 川芎嗪 补体系统 甘露糖结合凝集素 炎性因子 神经炎症 

分 类 号：R-332[医药卫生] R284.1R392.11R743.31R977.6