Liu Qiming, Shi Rui, Gu Yiting, Zhang Jiayun, Wang Shiduo, Xu Tiantian, Zhang Zhe, Tian Junbiao
Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, 050091, China.
Department of Neurology, The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, 050011, China.
BMC Neurol. 2025 May 6;25(1):196. doi: 10.1186/s12883-025-04205-5.
Ischemic stroke (IS) occurs when a blood clot obstructs a blood vessel supplying blood to the brain, leading to brain tissue damage due to insufficient oxygen and nutrients. The roles of immune cells and metabolites in IS are increasingly recognized, yet their specific mechanisms remain unclear.
This study conducted a comprehensive statistical analysis to explore the relationships between immune cell phenotypes, metabolite levels, and IS. We utilized methods such as inverse variance weighted (IVW), weighted median, and MR Egger to ensure robust results. Sensitivity analyses were performed to confirm the absence of significant heterogeneity or pleiotropy.
We identified several immune cell phenotypes significantly associated with IS. Notably, IgD + CD24 + AC showed a positive association with IS (OR = 1.045601, p = 0.011562), while CD62L- HLA DR + + monocyte AC demonstrated a negative association (OR = 0.948673, p = 0.005415). Among metabolites, adenosine 5'-monophosphate (AMP) to cysteine ratio was positively associated with IS (OR = 1.083144, p = 0.000310), whereas xanthurenate levels were negatively associated (OR = 0.926100, p = 0.001614). Mediation analysis revealed a significant mediating effect of acetylcarnitine levels on the relationship between IgD + CD24 + AC and IS, with an estimated mediation effect of 0.00606 (p = 0.036834077).
Our study highlights the crucial roles of specific immune cell phenotypes and metabolites in IS, suggesting their potential as novel therapeutic targets or biomarkers. The mediation analysis underscores the complex interactions between immune cells and metabolites in IS, providing valuable insights for future research. These findings pave the way for further exploration of the pathophysiological mechanisms and therapeutic strategies for IS.
当血凝块阻塞向大脑供血的血管时，就会发生缺血性中风（IS），导致脑组织因氧气和营养物质供应不足而受损。免疫细胞和代谢物在缺血性中风中的作用越来越受到认可，但其具体机制仍不清楚。
本研究进行了全面的统计分析，以探讨免疫细胞表型、代谢物水平与缺血性中风之间的关系。我们采用了逆方差加权（IVW）、加权中位数和MR Egger等方法，以确保结果的稳健性。进行了敏感性分析，以确认不存在显著的异质性或多效性。
我们确定了几种与缺血性中风显著相关的免疫细胞表型。值得注意的是，IgD+CD24+AC与缺血性中风呈正相关（OR=1.045601，p=0.011562），而CD62L-HLA DR++单核细胞AC呈负相关（OR=0.948673，p=0.005415）。在代谢物中，5'-单磷酸腺苷（AMP）与半胱氨酸的比值与缺血性中风呈正相关（OR=1.083144，p=0.000310），而黄尿酸水平呈负相关（OR=0.926100，p=0.001614）。中介分析显示，乙酰肉碱水平对IgD+CD24+AC与缺血性中风之间的关系具有显著的中介作用，估计中介效应为0.00606（p=0.036834077）。
我们的研究突出了特定免疫细胞表型和代谢物在缺血性中风中的关键作用，表明它们作为新型治疗靶点或生物标志物的潜力。中介分析强调了免疫细胞和代谢物在缺血性中风中的复杂相互作用，为未来的研究提供了有价值的见解。这些发现为进一步探索缺血性中风的病理生理机制和治疗策略铺平了道路。
