Galectin-3 作为缺血再灌注诱导急性肾损伤的早期生物标志物和潜在治疗靶点的转化研究。

A translational study of Galectin-3 as an early biomarker and potential therapeutic target for ischemic-reperfusion induced acute kidney injury.

机构信息

Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China.

Class 2017, School of Medicine, Nanchang University, Nanchang, Jiangxi Province, China.

出版信息

J Crit Care. 2021 Oct;65:192-199. doi: 10.1016/j.jcrc.2021.06.013. Epub 2021 Jul 2.

DOI:10.1016/j.jcrc.2021.06.013

PMID:34225083

Abstract

PURPOSE

We evaluated Galectin-3 (Gal-3) as a potential early biomarker of acute kidney disease (AKI), and the effect of Gal-3 inhibition by modified citrus pectin (P-MCP) on renal ischemia/reperfusion (I/R) induced AKI.

METHODS

Among fifty-two post-cardiac surgery patients, serum and urine Gal-3 levels were examined on intensive care unit (ICU) admission. In a rat renal I/R injury model, Gal-3 levels, renal function, and histopathology were evaluated in rats pretreated with P-MCP for one week (n = 16) compared to controls (n = 16).

RESULTS

Among post-cardiac surgery patients, median serum and urine Gal-3 levels on ICU admission were higher in patients who developed AKI than those who did not (AKI vs non-AKI serum: 18.37 vs. 8.08 ng/ml, p < 0.001; AKI vs non-AKI urine:13.27 vs. 6.27 ng/ml, p < 0.001). Serum and urine Gal-3 levels were reliable biomarkers for detecting AKI (AUC: 0.88 and 0.87). In the rat renal I/R injury model, I/R caused an increase of Gal-3 at 0.5 h after reperfusion (p < 0.05). Gal-3 inhibition by P-MCP significantly decreased Gal-3 release and expression (p < 0.05), reduced interleukin (IL-6) release (p < 0.05), decreased renal dysfunction, and reduced renal tubular injury.

CONCLUSIONS

Gal-3 is a potential early biomarker in the diagnosis of AKI. Inhibition of Gal-3 may provide therapeutic utility in the treatment of I/R-induced AKI.

摘要

目的

我们评估半乳糖凝集素-3（Gal-3）作为急性肾损伤（AKI）的潜在早期生物标志物，以及改性柑橘果胶（P-MCP）对肾缺血/再灌注（I/R）引起的 AKI 的抑制作用。

方法

在 52 例心脏手术后患者中，在重症监护病房（ICU）入院时检查血清和尿液 Gal-3 水平。在大鼠肾 I/R 损伤模型中，与对照组（n = 16）相比，用 P-MCP 预处理一周的大鼠（n = 16）评估 Gal-3 水平、肾功能和组织病理学。

结果

在心脏手术后患者中，发生 AKI 的患者 ICU 入院时的血清和尿液 Gal-3 水平中位数高于未发生 AKI 的患者（AKI 与非 AKI 血清：18.37 与 8.08ng/ml，p<0.001；AKI 与非 AKI 尿液：13.27 与 6.27ng/ml，p<0.001）。血清和尿液 Gal-3 水平是检测 AKI 的可靠生物标志物（AUC：0.88 和 0.87）。在大鼠肾 I/R 损伤模型中，再灌注后 0.5 小时 I/R 导致 Gal-3 增加（p<0.05）。P-MCP 抑制 Gal-3 释放和表达（p<0.05），减少白细胞介素（IL-6）释放（p<0.05），降低肾功能不全和肾小管损伤。