Department of Critical Care Medicine, Zhongnan Hospital, Wuhan University, Wuhan, Hubei Province, China.
School of Medicine, University of California, San Francisco, CA, USA.
Crit Care. 2021 Mar 18;25(1):109. doi: 10.1186/s13054-021-03538-0.
Galectin-3 (Gal-3) is a pleiotropic glycan-binding protein shown to be involved in sepsis and acute kidney injury (AKI). However, its role has never been elucidated in sepsis-associated AKI (S-AKI). We aimed to explore Gal-3's role and its potential utility as a therapeutic target in S-AKI.
In 57 patients admitted to the intensive care unit (ICU) with sepsis, serum Gal-3 was examined as a predictor of ICU mortality and development of AKI. In a rat model of S-AKI induced by cecal ligation and puncture (CLP), 7-day mortality and serum Gal-3, Interleukin-6 (IL-6), and creatinine were examined at 2, 8, and 24 hours (h) post-CLP. Two experimental groups received the Gal-3 inhibitor modified citrus pectin (P-MCP) at 400 mg/kg/day and 1200 mg/kg/day, while the control group received water only (n = 18 in each group).
Among 57 patients, 27 developed AKI and 8 died in the ICU. Serum Gal-3 was an independent predictor of AKI (OR = 1.2 [95% CI 1.1-1.4], p = 0.01) and ICU mortality (OR = 1.4 [95% CI 1.1-2.2], p = 0.04) before and after controlling for age, AKI, and acute physiology and chronic health evaluation (APACHE II) score. In the CLP rat experiment, serum Gal-3 peaked earlier than IL-6. Serum Gal-3 was significantly lower in both P-MCP groups compared to control at 2 h post-CLP (400 mg: p = 0.003; 1200 mg: p = 0.002), and IL-6 was significantly lower in both P-MCP groups at all time points with a maximum difference at 24 h post-CLP (400 mg: p = 0.015; 1200 mg: p = 0.02). In the Gal-3 inhibitor groups, 7-day mortality was significantly reduced from 61% in the control group to 28% (400 mg P-MCP: p = 0.03) and 22% (1200 mg P-MCP: p = 0.001). Rates of AKI per RIFLE criteria were significantly reduced from 89% in the control group to 44% in both P-MCP groups (400 mg: p = 0.007; 1200 mg: p = 0.007).
This translational study demonstrates the importance of Gal-3 in the pathogenesis of S-AKI, and its potential utility as a therapeutic target.
半乳糖凝集素-3（Gal-3）是一种具有多种生物活性的糖结合蛋白，已被证明与脓毒症和急性肾损伤（AKI）有关。然而，其在脓毒症相关 AKI（S-AKI）中的作用尚未阐明。我们旨在探讨 Gal-3 在 S-AKI 中的作用及其作为治疗靶点的潜在应用价值。
在因脓毒症入住重症监护病房（ICU）的 57 名患者中，检测血清 Gal-3 作为 ICU 死亡率和 AKI 发展的预测因子。在盲肠结扎和穿刺（CLP）诱导的 S-AKI 大鼠模型中，在 CLP 后 2、8 和 24 小时（h）检测 7 天死亡率和血清 Gal-3、白细胞介素-6（IL-6）和肌酐。两组实验动物分别接受半乳糖凝集素-3 抑制剂改性柑橘果胶（P-MCP）400mg/kg/天和 1200mg/kg/天治疗，对照组仅给予水（每组 18 只）。
在 57 名患者中，27 名患者发生 AKI，8 名患者在 ICU 死亡。血清 Gal-3 是 AKI（OR=1.2[95%CI 1.1-1.4]，p=0.01）和 ICU 死亡率（OR=1.4[95%CI 1.1-2.2]，p=0.04）的独立预测因子，在控制年龄、AKI 和急性生理学和慢性健康评估（APACHE II）评分之前和之后。在 CLP 大鼠实验中，血清 Gal-3 比 IL-6 更早达到峰值。与对照组相比，CLP 后 2 小时，两 P-MCP 组的血清 Gal-3 均显著降低（400mg：p=0.003；1200mg：p=0.002），且各时间点的 IL-6 均显著降低，以 24 小时时差异最大（400mg：p=0.015；1200mg：p=0.02）。在 Gal-3 抑制剂组中，7 天死亡率从对照组的 61%显著降低至 28%（400mg P-MCP：p=0.03）和 22%（1200mg P-MCP：p=0.001）。根据 RIFLE 标准，AKI 的发生率从对照组的 89%显著降低至两 P-MCP 组的 44%（400mg：p=0.007；1200mg：p=0.007）。
这项转化研究表明 Gal-3 在 S-AKI 发病机制中的重要性及其作为治疗靶点的潜在应用价值。
