黄芪甲苷通过调控 miR-17-3p/黏附素-1 保护剪切力诱导的糖萼损伤并减轻腹主动脉瘤。

Astragaloside IV Protects against Shear Stress-Induced Glycocalyx Damage and Alleviates Abdominal Aortic Aneurysm by Regulating miR-17-3p/Syndecan-1.

机构信息

Department of Vascular Surgery, Affiliated Hospital of Yunnan University, Kunming, Yunnan, China.

Department of Pharmaceutical Sciences, The Third People's Hospital of Yunnan Province, Kunming, China.

出版信息

Anal Cell Pathol (Amst). 2024 Feb 13;2024:2348336. doi: 10.1155/2024/2348336. eCollection 2024.

DOI:10.1155/2024/2348336

PMID:39290461

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11407896/

Abstract

BACKGROUND

The present study aimed to analyze the impact of astragaloside IV (AS-IV) on abdominal aortic aneurysm (AAA) and the glycocalyx, elucidating the potential mechanism of AS-IV.

METHODS

Rat models of AAA were established using porcine pancreatic elastase. The effects of intraperitoneal AS-IV injection on the morphology, diameter, and glycocalyx of the aorta and the expression of miR-17-3p and Syndecan-1 (SDC1) protein were examined. Differentially expressed miRNAs from peripheral blood samples of healthy individuals, untreated patients with AAA, and treated patients with AAA were identified through sequencing. The relationship between miR-17-3p and SDC1 was validated using a dual-luciferase reporter assay. In vitro, shear stress was induced in human aortic endothelial cells (HAECs) to simulate AAA. Overexpression of miR-17-3p was performed to assess the effects of AS-IV on miR-17-3p and SDC1 expressions, apoptosis, and glycocalyx in HAECs.

RESULTS

AS-IV mitigated aortic damage in AAA rats, reducing the aortic diameter and alleviating glycocalyx damage. In addition, it suppressed the increase in miR-17-3p expression and promoted SDC1 expression in AAA rats. Peripheral blood miR-17-3p levels were significantly higher in patients with AAA than in healthy individuals. miR-17-3p inhibited the SDC1 protein expression in HAECs. In the in vitro AAA environment, miR-17-3p was upregulated and SDC1 was downregulated in HAECs. AS-IV inhibited miR-17-3p expression, promoted SDC1 expression, and mitigated shear stress-induced apoptosis and glycocalyx damage in HAECs. Overexpression of miR-17-3p blocked AS-IV-induced SDC1 expression promotion, glycocalyx protection, and apoptosis suppression in HAECs.

CONCLUSION

miR-17-3p may damage the glycocalyx of aortic endothelial cells by targeting SDC1. AS-IV may promote SDC1 expression by inhibiting miR-17-3p, thereby protecting the glycocalyx and alleviating AAA.

摘要

背景

本研究旨在分析黄芪甲苷（AS-IV）对腹主动脉瘤（AAA）和糖萼的影响，阐明 AS-IV 的潜在机制。

方法

使用猪胰弹性蛋白酶建立大鼠 AAA 模型。通过腹腔内注射 AS-IV 观察其对主动脉形态、直径和糖萼以及 miR-17-3p 和 Syndecan-1（SDC1）蛋白表达的影响。通过测序鉴定来自健康个体、未经治疗的 AAA 患者和经治疗的 AAA 患者的外周血样本中的差异表达 miRNA。通过双荧光素酶报告基因实验验证 miR-17-3p 与 SDC1 的关系。在体外，通过诱导人主动脉内皮细胞（HAEC）的切应力来模拟 AAA。过表达 miR-17-3p 以评估 AS-IV 对 HAEC 中 miR-17-3p 和 SDC1 表达、细胞凋亡和糖萼的影响。

结果

AS-IV 减轻了 AAA 大鼠的主动脉损伤，降低了主动脉直径并减轻了糖萼损伤。此外，它抑制了 AAA 大鼠中 miR-17-3p 表达的增加，并促进了 SDC1 的表达。与健康个体相比，AAA 患者的外周血 miR-17-3p 水平显著升高。miR-17-3p 抑制了 HAEC 中的 SDC1 蛋白表达。在体外 AAA 环境中，HAEC 中的 miR-17-3p 上调，SDC1 下调。AS-IV 抑制 miR-17-3p 表达，促进 SDC1 表达，并减轻 HAEC 中切应力诱导的细胞凋亡和糖萼损伤。过表达 miR-17-3p 阻断了 AS-IV 诱导的 HAEC 中 SDC1 表达促进、糖萼保护和细胞凋亡抑制。