Department of Anesthesiology, Hainan General Hospital, Road Xiuhua, Haikou, Hainan Province, China.
Genes Genomics. 2021 Dec;43(12):1371-1379. doi: 10.1007/s13258-020-01019-2. Epub 2021 Jan 22.
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.
慢性阻塞性肺疾病（COPD）是一种慢性肺部疾病，也是世界上第三大致死原因。右美托咪定已被报道可有效抑制组胺诱导的支气管收缩。然而，COPD 中右美托咪定的分子机制尚未被发现。
探讨右美托咪定在 COPD 中的作用和机制，为 COPD 的临床治疗提供理论依据。
通过模拟物或抑制剂调节 miR-146a 的表达，实时 PCR 和 Western blot 检测人支气管上皮 16HBE 细胞中凋亡蛋白 p53、Bax 和 Bcl-2 的相对表达。用右美托咪定处理 16HBE 细胞和肺泡上皮 II 型细胞（AEC2），通过 TUNEL 和 Hoechst33342 染色检测细胞凋亡。通过吸烟建立 COPD 大鼠模型，检测右美托咪定对 COPD 进展的影响。通过 ELISA 检测血清中 IL-6、IL-1β 和 TNF-α 的水平，并检测右美托咪定处理的 COPD 大鼠模型中支气管肺泡灌洗液（BALF）的蛋白浓度。
miR-146a 促进 16HBE 细胞凋亡，降低细胞增殖。此外，右美托咪定通过降低 miR-146a 的表达，显示出减少 16HBEL 细胞凋亡的作用。此外，右美托咪定通过 miR-146a 调节 AEC2 细胞中的细胞凋亡和细胞凋亡。更重要的是，右美托咪定减轻了 COPD 大鼠模型的形态和病理学变化。
右美托咪定通过下调 miR-146a 减少 16HBE 细胞和 AEC2 细胞凋亡，减轻 COPD。
