[Assessment of histological changes in the lungs and Bax and Bcl-2 expression in bronchial epithelium, alveolar type 1 cells and neutrophils of rats in poisoning with baclofen].

Q4 Medicine
O L Romanova, M L Blagonravov, P G Dzhuvalyakov, V I Torshin, E Kh Barinov, A V Ershov, M A Kislov
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引用次数: 0

Abstract

Objective: To study the histological changes in lung of rats, evaluate their dynamics and determine the Bax and Bcl-2 genes expression in bronchial epithelium, alveolar type 1 cells and neutrophils at different times after the administration of baclofen.

Material and methods: The experiment was conducted on 20 mature (at the age of 20 weeks) male Wistar rats with a mass of 290-350 g, distributed in 4 groups (5 rats in each). Animals in the control group did not receive baclofen. Rats in experimental groups received baclofen at a dose of 85 mg/kg: in the 1st group, the experiment duration was 3 hours (time to maximum observed blood drug concentration); in the 2nd group - 4.5 h (drug half-life and time to maximum observed concentration of the main drug's metabolite - beta-[p-chlorophenyl])-gamma-hydroxybutyric acid in the blood); in the 3rd group - 24 h.

Results: A complex of pathological reactions developed in lungs of experimental animals when baclofen muscle relaxant was administered, namely circulatory disturbances at all levels of the microvasculature (venular and capillary congestion, hemorrhages in the interalveolar septums, alveoli, sludge), emphysema, sites of which punctuated with atelectases and dystelectases. The complex of pathological changes in the lungs had a certain dynamics and reached its highest severity by the 24th hour. Bax expression was strong, while Bcl-2 expression was moderate in the immunohistochemical (IHC) study of bronchical epithelium and alveolar type 1 cells, Bax and Bcl-2 expression in neutrophils was moderate in rats of the 1st group. The expression of Bax and Bcl-2 was strong in the bronchial epithelium and alveolar type 1 cells, the expression of Bax in neutrophils was moderate, and BCL-2 - strong in animals of the 2nd group. The expression of Bax in bronchial epithelium and alveolar type 1 cells was moderate, expression of Bcl-2 in bronchial epithelium and alveolar type 1 cells - strong, expression of Bax in neutrophils - weak and expression of Bcl-2 - strong among the rats of the 3rd group.

Conclusion: The complex of pathological changes in lungs had a certain dynamic. Data on the histological changes in lungs in combination with the results of the chemical study, can be used to diagnose the poisoning by baclofen and to establish the time since the drug was administered. The results obtained during the IHC study suggest the involvement of apoptosis in the development of lesion of bronchial epithelium and alveolar type 1 cells. In addition, the expression of Bcl-2 in epithelial cells may play a role in the process of their regeneration.

[巴氯芬中毒大鼠肺部组织学变化及支气管上皮细胞、肺泡 1 型细胞和中性粒细胞中 Bax 和 Bcl-2 表达的评估]。
研究目的研究巴氯芬给药后不同时间大鼠肺组织学变化,评估其动态变化,并测定支气管上皮、肺泡 1 型细胞和中性粒细胞中 Bax 和 Bcl-2 基因的表达:实验对象为 20 只成熟(20 周龄)的雄性 Wistar 大鼠,体重为 290-350 克,分为 4 组(每组 5 只)。对照组动物不接受巴氯芬治疗。实验组大鼠接受的巴氯芬剂量为 85 毫克/千克:第一组的实验持续时间为 3 小时(观察到血液中药物浓度最大值的时间);第二组为 4.5 小时(药物半衰期和观察到血液中主要药物代谢物-β-[对氯苯基])-γ-羟丁酸浓度最大值的时间);第三组为 24 小时:给实验动物服用巴氯芬肌肉松弛剂后,其肺部出现了复杂的病理反应,即各级微血管的循环障碍(静脉和毛细血管充血、肺泡间隔膜出血、肺泡淤血)、肺气肿,肺气肿部位伴有电解质酶和半电解质酶。肺部的病理变化具有一定的动态性,在第 24 小时达到最严重的程度。第一组大鼠支气管上皮细胞和肺泡 1 型细胞的免疫组织化学(IHC)研究显示,Bax 的表达较强,而 Bcl-2 的表达中等,中性粒细胞中 Bax 和 Bcl-2 的表达中等。第 2 组大鼠支气管上皮和肺泡 1 型细胞中的 Bax 和 Bcl-2 表达较强,中性粒细胞中的 Bax 表达中等,BCL-2 表达较强。第 3 组大鼠支气管上皮和肺泡 1 型细胞中 Bax 的表达为中等,支气管上皮和肺泡 1 型细胞中 Bcl-2 的表达为强,中性粒细胞中 Bax 的表达为弱,Bcl-2 的表达为强:肺部病理变化的复杂性具有一定的动态性。肺部组织学变化数据与化学研究结果相结合,可用于诊断巴氯芬中毒,并确定给药时间。IHC 研究的结果表明,支气管上皮细胞和肺泡 1 型细胞凋亡参与了病变的发展。此外,上皮细胞中 Bcl-2 的表达可能在其再生过程中发挥作用。
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来源期刊
Sudebno-Meditsinskaya Ekspertisa
Sudebno-Meditsinskaya Ekspertisa Medicine-Pathology and Forensic Medicine
CiteScore
0.60
自引率
0.00%
发文量
70
期刊介绍: The journal is concerned with the theory and practice of forensic medicine - the problems of thanatology, traumatology, toxicology, serology, forensic obstetrics, forensic dentistry, forensic psychiatry, forensic chemistry, physicotechnical methods of investigation, history of forensic medicine and some problems of criminology and legal laws related to forensic medicine. It publishes original studies by Russian authors, casuistry surveys, abstracts and reviews of Russian and foreign literature, scientific information, reports on scientific conferences.
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