Ma xing shi gan decoction eliminates PM2.5-induced lung injury by reducing pulmonary cell apoptosis through Akt/mTOR/p70S6K pathway in rats
| Autor: | Guang-hui Ren, Qiyang Yin, Ye-fang Wang, Jianping Zhu, Bo-wen Wang, Yunman Li, Yuxiang Fei, Bo Zhao, Weirong Fang |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Respiratory System Biophysics Plant Biology Cell Death & Injury Apoptosis PM2.5 Lung injury Biochemistry 03 medical and health sciences 0302 clinical medicine Western blot In vivo medicine Animals Humans lung injury Lung Molecular Biology Protein kinase B Research Articles PI3K/AKT/mTOR pathway bcl-2-Associated X Protein A549 cell Air Pollutants TUNEL assay medicine.diagnostic_test Chemistry Akt/mTOR/p70S6K pathway TOR Serine-Threonine Kinases Ribosomal Protein S6 Kinases 70-kDa Ma xing shi gan Decoction Cell Biology Therapeutics & Molecular Medicine Molecular biology Rats Disease Models Animal 030104 developmental biology Gene Expression Regulation Proto-Oncogene Proteins c-bcl-2 030220 oncology & carcinogenesis Particulate Matter Proto-Oncogene Proteins c-akt Drugs Chinese Herbal Signal Transduction |
| Zdroj: | Bioscience Reports |
| ISSN: | 1573-4935 0144-8463 |
| Popis: | The present study was designed to investigate the anti-apoptosis effect of Ma xing shi gan decoction (MXD) on PM2.5-induced lung injury via protein kinase B (Akt)/mTOR/p70S6K pathway. A UPLC-MS/MS system was introduced for component analysis of MXD. Rats were instilled with PM2.5 solution suspension intratracheally to induce acute lung injury. The rats were then orally administered with MXD (16, 8, and 4 g/kg) once a day for 7 consecutive days. The therapeutic effects of MXD were evaluated by Hematoxylin and Eosin (HE) staining. The apoptotic cell death was analyzed by terminal-deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay. The alterations in cytochrome c (Cytc) and cleaved-caspase-3 (C-caspase-3) were measured by immunohistochemistry (IHC). The expressions of Bax, B-cell lymphoma 2 (Bcl-2), p-Akt, p-mTOR and p-p70S6K were detected by Western blot. In vitro, PM2.5 exposure model was introduced in A549 cell, followed by incubation with MXD-medicated serum. Hoechst staining was used to determine apoptotic rate. The levels of Bax, Bcl-2, p-Akt, p-mTOR and p-p70S6K were detected by Western blot. Our results in vivo indicated that treatment with MXD decreased histopathological changes score, TUNEL-positive cells rate, expressions of Cytc and C-caspase-3. The in vitro results revealed that incubation with MXD-mediated serum decreased apoptotic rate. Both results in vivo and in vitro demonstrated that MXD inhibited pro-apoptotic protein Bax and promoted anti-apoptotic protein Bcl-2 expression. Likewise, MXD activated Akt/mTOR/p70S6K signal pathway, which was also confirmed by Western immunoblotting. In conclusion, MXD attenuates lung injury and the underlying mechanisms may relate to regulating the apoptosis via Akt/mTOR/p70S6K signaling pathway activation. |
| Databáze: | OpenAIRE |
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