银杏总黄酮与银杏总内酯对亚急性期卒中小鼠神经功能恢复促进作用的比较研究  

Comparative study on the effects of total ginkgo flavonol glycosides and total ginkgolides on neurofunctional recovery in mice with subacute stroke

作　　者：李志雄 肖光旭 贺爽[1,2] 王焕义 朱彦[1,2] LI Zhi-xiong;XIAO Guang-xu;HE Shuang;WANG Huan-yi;ZHU Yan(State Key Laboratory of Component-based Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Chinese Medicine New Drug Research and Development Center,Tianjin International Biomedical Research Institute,Tianjin 300457,China)

机构地区：[1]天津中医药大学,组分中药国家重点实验室,天津301617 [2]天津国际生物医药联合研究院,中药新药研发中心,天津300457

出　　处：《药学学报》2021年第1期231-243,共13页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81873037);国家重点研发计划项目(2018YFC1704502);天津中医药大学研究生科研创新资助项目(YJSKC20191035)。

摘　　要：舒血宁注射液作为一种银杏叶提取物制剂,在脑卒中急性期和亚急性期防治上表现出独特优势,但其主要活性部位尚不明晰。本研究旨在基于前期构建的小鼠脑卒中亚急性期模型,进一步探讨舒血宁的两个主要组分银杏总黄酮和银杏总内酯对促进脑卒中小鼠神经功能恢复的贡献度及作用机制。主要通过神经及行为学变化、脑梗死体积、血脑屏障渗透和脑水肿进行药效评价,结合转录组和网络药理学进行通路和靶标预测,最后在mRNA和蛋白水平进行机制验证。结果显示,在药效评价和粒细胞集落刺激因子(granulocyte colony-stimulating factor,GCSF)、巨噬细胞分化抗原1(macrophage-1 antigen,MAC-1)和E选择素参与的粒细胞黏附与浸润的调节机制中,银杏总内酯的作用均优于银杏总黄酮,提示舒血宁注射液可能主要通过银杏总内酯组分下调G-CSF介导的粒细胞黏附与浸润通路来改善亚急性期卒中小鼠的预后。这一发现有望为优化处方和寻找靶向治疗缺血性脑卒中预后的天然药物提供参考。本研究动物实验过程遵循天津中医药大学动物伦理委员会的规定。As a Ginkgo biloba extract preparation,shuxuening injection has a unique advantage in the preven‐tion and treatment of acute and subacute stroke,but its main active ingredient is still unclear.Using a subacute model of stroke in mice constructed earlier,we further explored the contribution and mechanism of the two main components of total ginkgo flavonol glycosides and total ginkgolides in facilitating the neurofunctional recovery in stroke-induced mice.The pharmacodynamics was mainly evaluated by neurobehavioral changes,cerebral infarc‐tion volume,blood-brain barrier permeability and brain edema.The pathway and targets were predicted by tran‐scriptome and network pharmacology.Finally,the mechanism was verified at the mRNA and protein levels.The results showed that the beneficial effect of total ginkgolides was greater than that of total ginkgo flavonol glycosides in both the pharmacodynamics and the regulatory mechanism of granulocyte adhesion and diapedesis involving granulocyte colony-stimulating factor(G-CSF),macrophage-1 antigen(MAC-1)and E-selectin.These findings suggest that shuxuening injection may improve the prognosis for mice with subacute stroke by down-regulating GCSF-mediated granulocyte adhesion and diapedesis pathway mainly through the total ginkgolide components.This finding is expected to provide reference for optimizing prescription and searching for natural drugs for targeting the treatment of ischemic stroke prognosis.The animal experiments in this study followed the regulations of Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine.

关 键 词：舒血宁注射液 银杏总黄酮 银杏总内酯 缺血性脑卒中 粒细胞集落刺激因子 

分 类 号：R964[医药卫生—药理学]