文章摘要
凌金颖,王琦,范海贞,戴婧雅,成小兰.黄芪桂枝五物汤改善大鼠局灶性脑缺血再灌注损伤:药理和代谢组学证据[J].南京中医药大学学报,2021,37(6):920-929.
黄芪桂枝五物汤改善大鼠局灶性脑缺血再灌注损伤:药理和代谢组学证据
Huangqi Guizhi Wuwu Decoction Ameliorates Focal Cerebral Ischemia-Reperfusion Injury in Rats: Pharmacological and Metabolomics Evidences
  
DOI:
中文关键词: 关键词:黄芪桂枝五物汤  脑缺血再灌注损伤  脑中动脉闭塞  代谢组学  UPLC/MS
英文关键词: Huangqi Guizhi Wuwu Decoction  cerebral ischemic-reperfusion  middle cerebral artery occlusion  metabolomics  UPLC/MS

基金项目:
作者单位
凌金颖1,王琦2,范海贞1,戴婧雅1,成小兰3 1.南京中医药大学附属中西医结合医院江苏 南京 2100282.南京道尔医药科技有限公司江苏 南京 210012
3.南京中医药大学中医学院·中西医结合学院
江苏 南京 210023 
摘要点击次数: 16
全文下载次数: 34
中文摘要:
      目的 研究黄芪桂枝五物汤对脑缺血损伤的神经保护作用,并探讨其可能作用机制。方法 将50只大鼠随机分为假手术组,模型组及黄芪桂枝五物汤低、中、高剂量组(5、10、20 g·kg-1),每组10只。除假手术组外,大鼠采用线栓法建立大脑中动脉闭塞(MCAO)模型。中药组大鼠灌胃给予复方水煎液,假手术组和模型组大鼠灌胃给予等量的生理盐水。连续灌胃7 d后,处死大鼠。通过神经功能缺损评分、脑梗死面积、脂质过氧化和炎症细胞因子水平检测来评估各组大鼠脑缺血性损伤程度。同时通过代谢组学研究黄芪桂枝五物汤对脑缺血再灌注损伤的可能机制。结果 黄芪桂枝五物汤可显著降低神经功能缺损评分和脑梗死面积,减少脂质过氧化和炎症细胞因子水平,表明其可有效减轻MCAO诱导的大鼠脑缺血性损伤。进一步的代谢组学研究表明,脑缺血再灌注损伤后血清代谢紊乱,共筛选和鉴定出23种与缺血性中风相关的代谢物发生显著性变化,是脑缺血潜在的生物标志物。代谢通路分析显示,MCAO主要通过靶向乙醛酸和二羧酸代谢,以及苯丙氨酸、酪氨酸和色氨酸的生物合成来诱导脑缺血性损伤。黄芪桂枝五物汤干预后,大部分代谢标记物发生了逆转,主要包括吲哚氧基硫酸、柠檬酸、3-羟基十二酸、3-甲基-2-丁烯酸、苹果酸、丁醛和尿酸等。结论 黄芪桂枝五物汤可有效改善大鼠局灶性脑缺血再灌注损伤,其发挥神经保护作用的机制可能与抑制炎症、改善多种代谢途径有关。
英文摘要:
      OBJECTIVE To investigate the neuroprotective effect of Huangqi Guizhi Wuwu Decoction (HGWD) on cerebral ischemia injury, and to explore the underlying mechanism.METHODS Fifty rats were randomly divided into 5 groups: sham operation group (sham), middle cerebral artery occlusion (MCAO) model group, and MCAO rats treated with HGWD at 5, 10, 20 g·kg-1. The first two groups were administered intragastrically (i.g.) with saline for 7 days, while HGWD groups were treated with HGWD at 5, 10, and 20 g·kg-1, correspondingly. The neurological deficits scores, cerebral infarct size, lipid peroxidation and inflammatory cytokines levels were used to evaluate the brain ischemic injury. The possible mechanism of HGWD on cerebral ischemia-perfusion injury was investigated by metabolomics. RESULTS HGWD treatment significantly attenuated middle cerebral artery occlusion (MCAO)-induced brain ischemic injury of rats as evidenced by decreasing the neurological deficits scores, cerebral infarct size, as well as lipid peroxidation and inflammatory cytokines levels. Further metabolomics study indicated that great metabolic disorders in serum were induced following cerebral ischemia/reperfusion injury. Totally 23 metabolites associated with ischemic stroke were proposed as potential biomarkers. The metabolic pathway analysis revealed that MCAO induced brain ischemic injuries mainly by targeting glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis. Correspondingly, HGWD could restore most of the imbalanced endogenous metabolites. CONCLUSION HGWD plays a protective role in focal cerebral ischemia-reperfusion injury in rats, which may be associated with the inhibition of inflammatory effect and improvement of multiple metabolic pathways.
查看全文   查看/发表评论  下载PDF阅读器
关闭
微信公众号