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吡咯烷二硫代氨基甲酸盐减轻博来霉素诱导的大鼠肺纤维化:对氧化应激、纤维化和炎症参数的调节

Pyrrolidinedithiocarbamate attenuates bleomycin-induced pulmonary fibrosis in rats: Modulation of oxidative stress, fibrosis, and inflammatory parameters.

作者信息

Zaafan Mai A, Zaki Hala F, El-Brairy Amany I, Kenawy Sanaa A

机构信息

a Pharmacology & Toxicology Department , Faculty of Pharmacy, October University for Modern Sciences and Arts , Cairo , Egypt.

b Pharmacology & Toxicology Department , Faculty of Pharmacy, Cairo University , Giza , Egypt.

出版信息

Exp Lung Res. 2016 Oct-Dec;42(8-10):408-416. doi: 10.1080/01902148.2016.1244578. Epub 2016 Oct 31.

DOI:10.1080/01902148.2016.1244578
PMID:27797599
Abstract

OBJECTIVE

The current study aimed to investigate the modulatory effects of pyrrolidinedithiocarbamate (PDTC; 100 mg/kg) on bleomycin-induced pulmonary fibrosis (5 mg/kg; intratracheal) in rats.

MATERIALS AND METHODS

Rats were randomly assigned to three groups: normal control, bleomycin control, and PDTC-treated groups. Lung injury was evaluated through histological examination, immunohistochemical detection of inducible nitric oxide synthase (iNOS) in lung tissue and evaluating the total and differential leucocytes count in bronchoalveolar lavage fluid. Lung tissue was used for biochemical assessment of lung content of hydroxyproline, transforming growth factor beta-1 (TGF-β1), tumor necrosis factor-alpha (TNF-α) as well as analysis of lipid peroxides, reduced glutathione (GSH), and total nitrite contents.

RESULTS

PDTC attenuated bleomycin-induced pulmonary fibrosis as evidenced by histological observations, decreased iNOS expression and prevention of bleomycin-induced altered total and differential leukocytes count. Additionally, PDTC caused a significant decrease in lung contents of hydroxyproline, TGF-β1, TNF-α, lipid peroxides, and total nitrite coupled with increase in lung GSH content as compared to bleomycin control group.

CONCLUSION

PDTC attenuated bleomycin-induced pulmonary fibrosis in rats via its anti-inflammatory, antioxidant, and antifibrotic activities.

摘要

目的

本研究旨在探讨吡咯烷二硫代氨基甲酸盐(PDTC;100毫克/千克)对博来霉素诱导的大鼠肺纤维化(5毫克/千克;气管内给药)的调节作用。

材料与方法

将大鼠随机分为三组:正常对照组、博来霉素对照组和PDTC治疗组。通过组织学检查、肺组织中诱导型一氧化氮合酶(iNOS)的免疫组化检测以及评估支气管肺泡灌洗液中的总白细胞和分类白细胞计数来评估肺损伤。肺组织用于对羟脯氨酸、转化生长因子β-1(TGF-β1)、肿瘤坏死因子-α(TNF-α)的肺含量进行生化评估,以及分析脂质过氧化物、还原型谷胱甘肽(GSH)和总亚硝酸盐含量。

结果

组织学观察表明,PDTC减轻了博来霉素诱导的肺纤维化,iNOS表达降低,且预防了博来霉素诱导的总白细胞和分类白细胞计数的改变。此外,与博来霉素对照组相比,PDTC使肺组织中的羟脯氨酸、TGF-β1、TNF-α、脂质过氧化物和总亚硝酸盐含量显著降低,同时肺GSH含量增加。

结论

PDTC通过其抗炎、抗氧化和抗纤维化活性减轻了博来霉素诱导的大鼠肺纤维化。

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