Galectin-3 在脓毒症急性肾损伤中的作用：一项转化研究。
Galectin-3 in septic acute kidney injury: a translational study.
机构信息
Department of Critical Care Medicine, Zhongnan Hospital, Wuhan University, Wuhan, Hubei Province, China.
School of Medicine, University of California, San Francisco, CA, USA.
出版信息
Crit Care. 2021 Mar 18;25(1):109. doi: 10.1186/s13054-021-03538-0.
BACKGROUND
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.
METHODS
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).
RESULTS
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).
CONCLUSIONS
This translational study demonstrates the importance of Gal-3 in the pathogenesis of S-AKI, and its potential utility as a therapeutic target.
背景
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。
方法
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）。
结果
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）。
结论
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。
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