以 3 毫克/千克的剂量通过气管内注射硫酸盐和氯化物形式的博莱霉素对 Sprague Dawley 大鼠进行肺纤维化建模的结果比较。

IF 4.3 3区 医学 Q2 CHEMISTRY, MEDICINAL Pharmaceuticals Pub Date : 2024-10-11 DOI:10.3390/ph17101360
Elena A Tukhovskaya, Yulia A Palikova, Mariya S Severyukhina, Alina M Ismailova, Victor A Palikov, Gulsara A Slashcheva, Natalya A Borozdina, Evgeniy S Mikhaylov, Irina N Kravchenko, Vitaly A Kazakov, Ekaterina N Kazakova, Elena A Kalabina, Ekaterina A Rasskazova, Maxim V Shinelev, Dmitry I Rzhevsky, Vladimir A Rykov, Igor A Dyachenko, Arkady N Murashev
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引用次数: 0

摘要

背景/目的:对实验室啮齿动物气管内注射博莱霉素(BLM)是一种标准的、广泛使用的肺纤维化(PF)模型技术。博莱霉素作为一种建模剂,主要以硫酸盐和氯化物两种盐的形式生产。我们比较了通过气管内注射硫酸 BLM 和氯化 BLM 在 SD 大鼠中建立肺纤维化模型的结果。方法:使用健康的成熟雄性 SD 大鼠。以 3 毫克/千克的剂量通过气管内注射硫酸 BLM 和氯化 BLM 来模拟 PF。PF 的发展标准包括体重增加、呼吸参数变化、相对肺重量、支气管肺泡液(BALF)的细胞成分、用三色马森染色法对 PF 的严重程度进行组织学评估。研究结果与对照组动物相比,气管内给药两种 BLM 盐会导致明显的 PF,这由所有测量参数的变化决定。在体重增加、羟脯氨酸含量和组织学评估方面,硫酸苯胺盐组和氯化苯胺盐组之间没有明显差异。然而,在 BALF 的细胞组成中发现了明显的差异--接受硫酸二甲基钴锰治疗的动物肺泡巨噬细胞和中性粒细胞水平明显增加。结论气管内给药两种BLM盐都会导致严重的肺结核;但是,接受硫酸盐BLM治疗的动物的炎症过程比接受氯化BLM治疗的动物更明显、更持久,前者在建模后21天以上观察到的炎症过程会导致更严重的肺结核。
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Comparison of the Results of Modeling Pulmonary Fibrosis in Sprague Dawley Rats by Intratracheal Administration of Bleomycin in the Form of Sulfate and Chloride at a Dose of 3 mg/kg.

Background/Objectives: Intratracheal administration of bleomycin (BLM) to laboratory rodents is a standard, widely used technique used to model pulmonary fibrosis (PF). BLM, as a modeling agent, is produced mainly in the form of two salts-sulfate and chloride. We compared the results of modeling PF in SD rats by intratracheal administration of BLM sulfate and BLM chloride. Methods: Healthy mature male SD rats were used. PF was modeled by intratracheal administration of BLM sulfate and BLM chloride at a dose of 3 mg/kg. The criteria for the development of PF included body weight gain, changes in respiratory parameters, relative lung weight, cellular composition of broncho-alveolar fluid (BALF), histological assessment of the severity of PF with trichrome Masson staining. Results: Intratracheal administration of both BLM salts led to the development of pronounced PF, which was determined by changes in all of the measured parameters relative to control animals. There were no significant differences between the BLM sulfate and BLM chloride groups in body weight gain, hydroxyproline content, and histological evaluation. However, significant differences were identified in the cellular composition of BALF-a significant increase in alveolar macrophages and neutrophils levels in animals treated with BLM sulfate. Conclusions: Intratracheal administration of both BLM salts led to the development of severe PF; however, the inflammatory process in animals receiving BLM sulfate was more pronounced and prolonged than in animals receiving BLM chloride, which in the former, when observed more than 21 days after modeling, can lead to more severe PF.

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来源期刊
Pharmaceuticals
Pharmaceuticals Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.10
自引率
4.30%
发文量
1332
审稿时长
6 weeks
期刊介绍: Pharmaceuticals (ISSN 1424-8247) is an international scientific journal of medicinal chemistry and related drug sciences.Our aim is to publish updated reviews as well as research articles with comprehensive theoretical and experimental details. Short communications are also accepted; therefore, there is no restriction on the maximum length of the papers.
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