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气管内递送间充质干细胞条件培养基通过抑制哮喘大鼠细胞凋亡改善病变。

Intra-tracheal delivery of mesenchymal stem cell-conditioned medium ameliorates pathological changes by inhibiting apoptosis in asthmatic rats.

机构信息

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Mol Biol Rep. 2022 May;49(5):3721-3728. doi: 10.1007/s11033-022-07212-8. Epub 2022 Feb 3.

DOI:10.1007/s11033-022-07212-8
PMID:35118570
Abstract

BACKGROUND

Asthma, an inflammatory illness of the lungs, remains the most common long-term disease amongst children. This study tried to elaborate the status of apoptosis in asthmatic pulmonary niche after the application of rat mesenchymal stem cells (MSC-CM)-derived secretome.

METHODS AND RESULTS

Here, we randomly allocated male Wistar rats into three groups (n = 8); Control animals were intratracheally given 50 μl vehicle. In control-matched sensitized rats, 50 μl normal saline was used. In the last group, 50 μl MSC-CM was applied. Two-week post-administration, transcription of T-bet, GATA-3, Bax, Bcl-2 and Caspase-3 was measured by gene expression analysis. Pathological injuries were monitored using H&E staining. The BALF level of TNF-α was measured using ELISA assay. In asthmatic rats received MSC-CM, the expression of T-bet was increased while the level of GATA-3 decreased compared to the S group (p < 0.05). Levels of BALF TNF-α were suppressed in asthmatic niche after MSC-CM administration (p < 0.05). Compared to the asthmatic group, MSC-CM had potential to alter the expression of apoptosis-related genes in which the expression of Bax and Caspase 3 was decreased and the expression of pro-survival factor, Bcl-2 increased (p < 0.05).

CONCLUSION

Our data notified the potency of direct administration of MSC-CM in the alleviation of airway inflammation, presumably by down regulating apoptotic death in pulmonary niche.

摘要

背景

哮喘是一种肺部炎症性疾病,仍是儿童中最常见的慢性疾病。本研究试图阐述大鼠间充质干细胞(MSC-CM)衍生的分泌组应用后哮喘肺龛中的细胞凋亡状态。

方法和结果

我们将雄性 Wistar 大鼠随机分为三组(n=8);对照组气管内给予 50μl 载体。在对照匹配的致敏大鼠中,使用 50μl 生理盐水。在最后一组中,应用 50μl MSC-CM。给药后 2 周,通过基因表达分析测量 T-bet、GATA-3、Bax、Bcl-2 和 Caspase-3 的转录。通过 H&E 染色监测病理损伤。使用 ELISA 测定 BALF 中 TNF-α 的水平。在接受 MSC-CM 的哮喘大鼠中,与 S 组相比,T-bet 的表达增加,而 GATA-3 的水平降低(p<0.05)。在 MSC-CM 给药后,哮喘龛中的 BALF TNF-α 水平受到抑制(p<0.05)。与哮喘组相比,MSC-CM 有可能改变与细胞凋亡相关的基因表达,其中 Bax 和 Caspase 3 的表达降低,而生存因子 Bcl-2 的表达增加(p<0.05)。

结论

我们的数据通知了直接给予 MSC-CM 缓解气道炎症的潜力,可能通过下调肺龛中的细胞凋亡死亡。

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