Migraine is a chronic episodic neurovascular disease with a distinct"episode-remission"feature.According to the theory of traditional Chinese medicine,migraine belongs to the class of diseases including"Toutong"and"Toufeng".Disorder of qi and blood,especially blood stasis due to qi deficiency,lie at the basis of migraine pathogenesis.The physiological function of the neurovascular unit is strongly related to qi and blood.Focusing on the neurovascular unit,this paper expounds the physiological basis of the theory of qi and blood from the perspective of microenvironment homeostatic disorder and the interaction of various cell components,and discusses the scientific connotation of the pathogenesis of qi and blood in migraine.Disordered homeostasis of the neurovascular unit is involved in the pathology of migraine and tallies with the pathogenesis of qi and blood in migraine,which is mainly reflected in dysfunction of astringing,defending,and transforming due to qi deficiency,as well as pathogenic toxin accumulation and blood stasis.The explanation based on homeostasis of the neurovascular unit due to qi and blood pathogenesis in migraine is helpful to understand the development of migraine integrally and to provide guidance for traditional Chinese medicine treatment and research of migraine from the theory of qi and blood.

Objective:The Qinzhi Zhudan formula(QZZD)exhibits a prominent therapeutic effect in the treatment of vascular dementia(VaD).This study combined a network pharmacology approach and experimental validation to identify the underlying biological mechanism of QZZD against VaD.Methods:Male Wistar rats received bilateral common carotid artery occlusion(BCCAO)surgery,and after 4 weeks of intragastric administration of QZZD,the therapeutic effect was assessed using the Morris water maze test and cerebral blood flow(CBF)assessment.Hematoxylin and eosin staining,Nissl staining,and electron microscopy were used to measure the histopathological changes in the neurons of rats.The effect of QZZD treatment on hippocampal neurotransmitters was assessed by high-performance liquid chromatography with electrochemical detection and liquid chromatography mass spectrometry.Immunofluorescence was used to observe VaD-induced microglia activation.The inflammatory cytokine levels were assessed by enzyme linked immunosorbent assay.Western blot was used to examine the TNFR1-mediated TNF pathway,which was screened out by network pharmacology analysis.Results:QZZD treatment alleviated pathological changes and neuronal damage in VaD rats and atten-uated their cognitive impairment.In addition,QZZD increased CBF and the expression of acetylcholine and 5-hydroxytryptamine in the hippocampal region.Notably,QZZD inhibited microglial activation and the expression of IL-6 and TNF-a.Network pharmacology and western blot indicated that QZZD inhibited the levels of TNFR1,NF-KBp65,p-ERK,TNF-α,and IL-6,which are related to the TNFR1-mediated TNF signaling pathway.Conclusion:QZZD clearly improved learning and memory function,reduced brain pathological damage,elevated CBF and hippocampal neurotransmitter levels,and alleviated neuroinflammation of VaD rats partly by inhibiting the TNFR1-mediated TNF pathway,indicating its potential value in the clinical therapy of VaD.