1. Dexmedetomidine targets miR-146a and participates in the progress of chronic obstructive pulmonary disease in vivo and in vitro
- Author
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Duozhi Wu, Dandan Xing, Lu Xiong, Shuang-Feng Li, Ye-Hua Wu, Tiejun Li, Na Li, and Qiuchang Li
- Subjects
0106 biological sciences ,0301 basic medicine ,Interleukin-1beta ,Apoptosis ,Respiratory Mucosa ,Pharmacology ,Biology ,01 natural sciences ,Biochemistry ,Cell Line ,Rats, Sprague-Dawley ,Pulmonary Disease, Chronic Obstructive ,03 medical and health sciences ,Western blot ,Genetics ,medicine ,Animals ,Humans ,Dexmedetomidine ,Molecular Biology ,Cells, Cultured ,Cell Proliferation ,COPD ,TUNEL assay ,medicine.diagnostic_test ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Cell growth ,medicine.disease ,Rats ,respiratory tract diseases ,MicroRNAs ,030104 developmental biology ,Bronchoalveolar lavage ,Bronchoconstriction ,medicine.symptom ,010606 plant biology & botany ,medicine.drug - Abstract
Chronic obstructive pulmonary disease (COPD) is a chronic lung disease and the third leading cause of death in the world. Dexmedetomidine has been reported to effectively inhibit histamine-induced bronchoconstriction. However, the molecular mechanism of dexmedetomidine in COPD has not been found. To explore the role and mechanism of dexmedetomidine in COPD, and to provide theoretical basis for clinical treatment of COPD. The expression of miR-146a was regulated by mimics or inhibitor and the relative expression of apoptotic proteins p53, Bax and Bcl-2 in human bronchial epithelial 16HBE cells was determined by real-time PCR and Western blot. Dexmedetomidine was treated for 16HBE cells and alveolar epithelial type II cells (AEC2), the cell apoptosis was detected by TUNEL and Hoechst33342 staining. A COPD rat model was established by smoking to test the effects of dexmedetomidine on the progression of COPD. The levels of IL-6, IL-1β and TNF-α in serum were measured by ELISA and the protein concentration of bronchoalveolar lavage fluid (BALF) was also detected in dexmedetomidine treated COPD rat model. miR-146a promoted 16HBE cell apoptosis and reduced cell proliferation. Additionally, dexmedetomidine was showed to reduce the 16HBEL cell apoptosis through reducing the expression of miR-146a. Moreover, dexmedetomidine regulated cell apoptosis and cell apoptosis through miR-146a in AEC2 cells. More importantly, dexmedetomidine attenuated the morphology and pathology of COPD rat model. Dexmedetomidine reduced 16HBE cells and AEC2 cell apoptosis and attenuated COPD by down-regulating miR-146a.
- Published
- 2021