舒洛地特对阻塞性黄疸小鼠模型急性肺损伤的保护作用。
The Protective Effect of Sulodexide on Acute Lung Injury Induced by a Murine Model of Obstructive Jaundice.
机构信息
Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing, China.
Anesthesia and Operation Center, Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
出版信息
Biomed Res Int. 2022 Aug 26;2022:8717950. doi: 10.1155/2022/8717950. eCollection 2022.
INTRODUCTION
The effect of sulodexide (SLX) on obstructive jaundice- (OJ-) induced acute lung injury (ALI) in rats was examined in this study.
METHODS
In this study, 48 rats were randomly assigned to one of six groups: sham, OJ, OJ+saline, OJ+SLX (0.5 mg/ml/d), OJ+SLX (1 mg/ml/d), and OJ+SLX (2 mg/ml/d). The pathological lung injury was assessed by histological analysis and lung injury grading. ELISA kits were used to evaluate the expression of IL-6, IL-1, TNF-, and syndecan-1 (SDC-1) in bronchoalveolar lavage fluids (BALFs). Commercial assay kits were performed to evaluate malondialdehyde (MDA) production and catalase (CAT) activity in lung tissues. The apoptosis was assessed by TUNEL assay. The lung microvascular permeability was investigated using Evans blue leakage, lung wet/dry weight (W/D) ratio, and lung permeability index (LPI). SDC-1, claudin-5, ZO-1, and VE cadherin expression levels in lung tissues were measured using Western blot.
RESULTS
The OJ-induced ALI rats showed severe lung injury. The value of IL-6, IL-1, TNF-, and SDC-1 in BALFs was remarkedly increased in the OJ group. MDA content, apoptotic area, apoptotic molecules, and SDC-1 level were all higher in the OJ group's lung tissues than in the sham group. CAT activity, Evans blue leakage, W/D ratio, LPI, and expression of claudin-5, ZO-1, and VE cadherin were all lower in the OJ group compared to the sham group. The degenerative alterations in lung tissue improved after 7 days of treatment with 2 mg/ml SLX. The BALFs had lower amounts of IL-6, IL-1, TNF-, and SDC-1. The SLX therapy reduced MDA levels while restoring CAT activity. In lung tissues, SLX reduced apoptotic area and SDC-1 expression. SLX reduced lung microvascular permeability by raising the expression of Claudin-5, ZO-1, and VE-cadherin in lung tissue when compared to the OJ group.
CONCLUSION
The results suggested that SLX attenuates OJ-induced ALI in rats by protecting the pulmonary microvascular endothelial barrier.
简介
本研究旨在探讨舒洛地特（SLX）对大鼠梗阻性黄疸（OJ）诱导的急性肺损伤（ALI）的影响。
方法
本研究将 48 只大鼠随机分为六组：假手术组、OJ 组、OJ+生理盐水组、OJ+SLX（0.5mg/ml/d）组、OJ+SLX（1mg/ml/d）组和 OJ+SLX（2mg/ml/d）组。通过组织学分析和肺损伤分级评估病理性肺损伤。使用酶联免疫吸附试验（ELISA）试剂盒评估支气管肺泡灌洗液（BALF）中白细胞介素 6（IL-6）、白细胞介素 1（IL-1）、肿瘤坏死因子-α（TNF-α）和硫酸乙酰肝素蛋白聚糖-1（SDC-1）的表达。采用商业分析试剂盒评估肺组织中丙二醛（MDA）生成和过氧化氢酶（CAT）活性。通过 TUNEL 检测评估细胞凋亡。通过 Evans 蓝渗漏、肺湿/干重（W/D）比和肺通透性指数（LPI）评估肺微血管通透性。采用 Western blot 法检测肺组织中 SDC-1、闭合蛋白-5（claudin-5）、紧密连接蛋白-1（ZO-1）和血管内皮钙黏蛋白（VE 钙黏蛋白）的表达水平。
结果
OJ 诱导的 ALI 大鼠表现出严重的肺损伤。OJ 组 BALF 中 IL-6、IL-1、TNF-α 和 SDC-1 的含量显著升高。OJ 组肺组织中 MDA 含量、细胞凋亡面积、凋亡分子和 SDC-1 水平均高于假手术组。与假手术组相比，OJ 组 CAT 活性、Evans 蓝渗漏、W/D 比、LPI 以及 claudin-5、ZO-1 和 VE 钙黏蛋白的表达均较低。7 天 2mg/ml SLX 治疗后，肺组织的退行性改变得到改善。BALF 中的 IL-6、IL-1、TNF-α 和 SDC-1 含量降低。SLX 治疗降低 MDA 水平，同时恢复 CAT 活性。在肺组织中，SLX 通过提高肺组织中 Claudin-5、ZO-1 和 VE-cadherin 的表达来降低细胞凋亡面积和 SDC-1 表达。与 OJ 组相比，SLX 降低了肺微血管通透性。
结论
本研究结果表明，SLX 通过保护肺微血管内皮屏障来减轻大鼠 OJ 诱导的 ALI。
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