槲皮素可改善肝肺综合征大鼠模型的急性肺损伤。

Quercetin ameliorates acute lung injury in a rat model of hepatopulmonary syndrome.

机构信息

Assistant Professor of Physiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

Lecturer of Anatomy, Rabigh Faculty of Medicine, King Abdulaziz University, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

出版信息

BMC Complement Med Ther. 2022 Dec 3;22(1):320. doi: 10.1186/s12906-022-03785-w.

DOI:10.1186/s12906-022-03785-w

PMID:36463144

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9719635/

Abstract

BACKGROUND

Common bile duct ligation (BDL) is a rat experimental model to induce biliary cirrhosis. Lung fibrosis and pulmonary vascular angiogenesis and congestion are the most common complications of biliary cirrhosis that is known as hepatopulmonary syndrome. The aim of the present work is to investigate the acute lung injury in a BDL model and to investigate the possible protective effect of quercetin on this injury.

METHODS

Twenty-four adult male albino rats of the Wister strain (weighing 150-250 g). Animals were divided into 3 groups, with 8 rats each: Group I: Sham-operated group (control). Group II: Bile duct ligation group (BDL) sacrificed after 28 days from the surgery. Group III: Quercetin-treated bile duct ligation group (Q-BDL) was given orally by gastric gavage in a dose of 50 mg/kg/day, starting from the 4th day of the operation until the 28th day. At the end of the experiment, at day 28, all rats were sacrificed. Lung specimens were processed to measure Endothelin B receptor gene expression by PCR, lung surfactant by ELISA, "eNO" s by immunohistochemistry. Histological assessment was done using; H&E, Masson's trichrome, PAS, toluidine blue-stained semi-thin sections, transmission electron microscope. Histomorphometric and statistical studies were done.

RESULTS

BDL group showed significant increase in lung index together with mononuclear cellular infiltration denoting lung inflammatory state. Also, the significant increase in pulmonary endothelial nitric oxide synthase ("eNO" s) area percent and endothelin B receptor (ET) gene expression indicates enhanced angiogenesis. Pulmonary surfactant concentration was significantly decreased together with thickening of interalveolar septa denoting lung injury and fibrosis. Quercetin led to significant decrease in lung index, pulmonary "eNO" s area percent, ET gene expression and significant increase in pulmonary surfactant concentration. Quercetin treatment improved histological changes and morphometric measurements, limited mononuclear cellular infiltration and decreased perivascular and perialveolar collagen deposition.

CONCLUSION

Quercetin ameliorates the hepatopulmonary syndrome-induced lung injury through its anti-inflammatory, antioxidative and antifibrotic effects.

摘要

背景

胆总管结扎（BDL）是一种诱导胆汁性肝硬化的大鼠实验模型。肺纤维化和肺血管生成及淤血是胆汁性肝硬化最常见的并发症，被称为肝肺综合征。本研究旨在探讨 BDL 模型中的急性肺损伤，并研究槲皮素对这种损伤的可能保护作用。

方法

24 只成年雄性白化 Wister 大鼠（体重 150-250g）。动物分为 3 组，每组 8 只：第 1 组：假手术组（对照组）。第 2 组：胆管结扎组（BDL），手术后 28 天处死。第 3 组：槲皮素治疗胆管结扎组（Q-BDL），术后第 4 天开始每天灌胃给予 50mg/kg 槲皮素，直至第 28 天。实验结束时，即第 28 天，所有大鼠均被处死。处理肺标本，通过 PCR 测量内皮素 B 受体基因表达，通过 ELISA 测量肺表面活性剂，通过免疫组化测量“eNO”s。使用 H&E、Masson 三色、PAS、甲苯胺蓝染色半薄切片、透射电镜进行组织学评估。进行组织形态计量学和统计学研究。

结果

BDL 组肺指数显著增加，伴有单核细胞浸润，提示肺部炎症状态。此外，肺内皮型一氧化氮合酶（“eNO”s）面积百分比和内皮素 B 受体（ET）基因表达的显著增加表明血管生成增强。肺表面活性剂浓度显著降低，肺泡间隔增厚，提示肺损伤和纤维化。槲皮素导致肺指数、肺“eNO”s 面积百分比、ET 基因表达显著降低，肺表面活性剂浓度显著升高。槲皮素治疗改善了组织学变化和形态计量学测量，限制了单核细胞浸润，并减少了血管周围和肺泡周围胶原沉积。