GZMK-免疫炎症轴在高血压中的 调控作用

Regulatory Role of the GZMK-Immune Inflammatory Axis in Hypertension

摘要: 目的：探讨颗粒酶K (granzyme K, GZMK)在高血压中的表达特征及其与免疫炎症指标CD4、白细胞介素-6 (interleukin-6, IL-6)、肿瘤坏死因子-α (tumor necrosis factor-α, TNF-α)的关系，并分析上述指标在GZMK与高血压之间的中介作用。方法：收集研究对象临床资料及相关检测指标，比较不同组间GZMK及免疫炎症指标水平差异。采用散点图结合局部加权回归平滑(LOESS)曲线分析GZMK与CD4、IL-6及TNF-α之间的相关趋势，并构建中介效应模型，评价CD4、IL-6及TNF-α在GZMK与高血压之间的中介作用。结果：高血压组GZMK水平高于对照组，且CD4、IL-6及TNF-α水平亦呈升高趋势。相关性分析显示，GZMK与CD4、IL-6及TNF-α均呈正向变化趋势。中介效应分析结果显示，CD4、IL-6及TNF-α在GZMK与高血压之间均存在显著中介作用，其中TNF-α的中介效应最强。结论：GZMK升高与高血压相关免疫炎症反应增强密切相关，并可能通过CD4、IL-6及TNF-α介导的免疫炎症通路参与高血压的发生发展。GZMK有望成为高血压免疫炎症研究中的潜在生物学标志物。

Abstract: Objective: To investigate the expression characteristics of granzyme K (GZMK) in hypertension and its relationships with immune-inflammatory indicators, including CD4, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and to further analyze the mediating effects of these indicators on the association between GZMK and hypertension. Methods: Clinical data and related laboratory indicators were collected from the study subjects. Differences in GZMK and immune-inflammatory indicators between groups were compared. Scatter plots combined with locally estimated scatterplot smoothing (LOESS) curves were used to analyze the correlation trends between GZMK and CD4, IL-6, and TNF-α. In addition, a mediation effect model was constructed to evaluate the mediating roles of CD4, IL-6, and TNF-α in the relationship between GZMK and hypertension. Results: The level of GZMK was higher in the hypertension group than in the control group, and the levels of CD4, IL-6, and TNF-α also showed an increasing trend. Correlation analysis showed that GZMK was positively associated with CD4, IL-6, and TNF-α. Mediation analysis further demonstrated that CD4, IL-6, and TNF-α all had significant mediating effects on the association between GZMK and hypertension, among which TNF-α showed the strongest mediating effect. Conclusion: Elevated GZMK is closely associated with enhanced immune-inflammatory responses in hypertension and may participate in the development and progression of hypertension through immune-inflammatory pathways mediated by CD4, IL-6, and TNF-α. GZMK may serve as a potential biomarker in studies of immune inflammation in hypertension.