中文摘要
缺血性脑卒中(IS)是我国主要疾病负担之一,尽管被广泛研究但仍然缺乏有效的预警标志物。项目组发现免疫球蛋白G(IgG) N-糖基化异常与IS的主要危险因素(高血压、高脂血症及糖尿病)关联,而IgG通过糖基修饰调控炎症且炎症是动脉粥样硬化性狭窄和IS的主要机制;因此假设“IgG N-糖基化异常是IS发病的早期事件(正常或无症状脑动脉狭窄阶段),其通过调控炎症信号通路,影响IS的发生”。本研究拟采用横断面研究调查血浆IgG N-糖基组与脑动脉狭窄(CAS)或炎症标志物的关联;在前瞻性人群队列中采用巢式病例对照方法探索基线IgG N-糖基组与随访中首发IS的关联,筛选可以用于IS发病风险分层的糖基生物标志物,建立包含传统危险因素、炎症和糖基标志物的IS发病预警模型。本研究首次在人群水平上探讨IgG糖基与炎症状态、CAS及IS发病的关联,将为IS高危人群筛选提供方法并可能发现IS干预性预防的靶点。
英文摘要
Ischemic stroke (IS) is one of the major public health challenges, and will worsen with the increasing incidence of hypertension, hyperglycaemia and hyperlipoidemia; therefore early prediction is of important significance for the prevention of IS. Based on 1) the recognized inflammatory mechanism of IS, 2) N-glycan of immunoglobulin G (IgG) regulates the inflammatory pathways, 3) our findings that the plasma IgG N-glycan associated with hypertension, hyperglycaemia and hyperlipoidemia (the first, ninth and second risk factors of ischemic stroke, and 4) our findings that inflammatory biomarkers Lp-PLA2 associate with cerebral artery atherosclerotic stenosis (CAS) and contribute to the incidence of IS, we hypothesized that abnormal IgG N-glycosylation is the early events of IS, which associate with CAS and function in inflammatory pathways, and finally lead to the occurrence of IS. In this community based prospective cohort, we will investigate the association between IgG N-glycome and CAS or inflammatory biomarkers based on a cross-sectional study, and investigate the association between baseline IgG N-glycome and incidence of IS based on a nested case-control study. We firstly attempt to determine the relation between IgG glycosylation and inflammation state at the population level, and firstly try to screen the IgG glycome biomarkers for risk stratification of ischemic stroke. The study may find novel glycans biomarkers for ischemic stroke, and provide predicated model for screening of high-risk population of ischemic stroke.
