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暴露于不同剂量石棉粉尘的大鼠血液中的分子和免疫变化。

Molecular and immunological changes in blood of rats exposed to various doses of asbestos dust.

机构信息

Department of General Biology and Genomics, L.N. Gumilyov Eurasian National University, 010008, 2 Satpayev Str., Nur-Sultan, Republic of Kazakhstan.

Department of General Biology and Genomics, L.N. Gumilyov Eurasian National University, 010008, 2 Satpayev Str., Nur-Sultan, Republic of Kazakhstan.

出版信息

Cytokine. 2022 Nov;159:156016. doi: 10.1016/j.cyto.2022.156016. Epub 2022 Aug 30.

Abstract

BACKGROUND

Asbestos-related diseases are a group of diseases resulting from the inhalation of asbestos fibres and their subsequent deposition in the lung parenchyma, which causes the development of inflammatory and fibrotic processes in the respiratory system. Cases of the disease often occur in the practice of doctors.

AIMS

The purpose of the study was to examine the level of circulating-free mitochondrial DNA (cf mtDNA), pro-inflammatory cytokines, immunological status and structural changes in the lung of rats exposed to various doses of asbestos dust.

METHODS

Immune monitoring was performed using the peripheral blood samples of 40 male Wistar rats exposed and unexposed to asbestos dust. cf mtDNA copy numbers were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and cytokines were determined using a rat Enzyme Linked Immuno Sorbent Assay (ELISA) kit.

RESULTS

A comprehensive assessment of the histopathological study performed under exposure to asbestos at a dose of 25 mg and 50 mg showed the presence of pronounced structural defects in the lung tissue of laboratory rats. The level of cf mtDNA in plasma of rats exposed to asbestos at a dose of 25 mg was reliably higher than that of control rats, and animals exposed to asbestos at a dose of 50 mg. The highest levels of pro-inflammatory cytokines IL-6 and TNF-a were also observed after asbestos dusting at a dose of 25 mg.

CONCLUSIONS

According to the results of the immunological status obtained, the decrease in the levels of pro-inflammatory cytokines in the blood plasma at 50 mg is due to the immunosuppressive effect in the rat immune system at this dose. A positive correlation was found between TNF-a level and copy numbers of cf mtDNA at a dose of 25 mg.

摘要

背景

石棉相关疾病是一组由吸入石棉纤维及其随后在肺实质中的沉积引起的疾病,导致呼吸系统中发生炎症和纤维化过程。这种疾病的病例在医生的实践中经常出现。

目的

本研究的目的是检查暴露于不同剂量石棉粉尘的大鼠循环游离线粒体 DNA(cf mtDNA)、促炎细胞因子、免疫状态和肺结构变化的水平。

方法

使用暴露和未暴露于石棉粉尘的 40 只雄性 Wistar 大鼠的外周血样本进行免疫监测。使用定量实时聚合酶链反应(qRT-PCR)检测 cf mtDNA 拷贝数,并使用大鼠酶联免疫吸附测定(ELISA)试剂盒测定细胞因子。

结果

在暴露于 25mg 和 50mg 剂量的石棉下进行的组织病理学研究的综合评估显示,实验室大鼠的肺组织存在明显的结构缺陷。暴露于 25mg 剂量石棉的大鼠血浆中 cf mtDNA 的水平明显高于对照组大鼠,而暴露于 50mg 剂量石棉的大鼠则更高。在 25mg 剂量的石棉粉尘处理后,也观察到促炎细胞因子 IL-6 和 TNF-a 的水平最高。

结论

根据获得的免疫状态结果,在 50mg 剂量下血液血浆中促炎细胞因子水平的降低是由于在此剂量下大鼠免疫系统的免疫抑制作用。在 25mg 剂量下,TNF-a 水平与 cf mtDNA 的拷贝数之间存在正相关关系。

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