Department of Respiratory Medicine, Second People's Hospital of Yueqing, Zhejiang Province, China.
Clinical Laboratory, Second People's Hospital of Yueqing, Zhejiang Province, China.
Bioengineered. 2022 Feb;13(2):4137-4145. doi: 10.1080/21655979.2021.2011013.
Carvedilol possess multiple functions such as antioxidation and neuroprotection RhoA/ROCK is reported to participate in acute lung injury (ALI). The aim of the present study was to explore the role of carvedilol in LPS-induced ALI. BEAS2B cells were subjected to LPS for the construction of in vitro ALI model. After that, the protective effects of carvedilol were evaluated by Cell Counting Kit-8 (CCK-8). The activities of RhoA/ROCK were then measured to confirm its association with carvedilol by quantitative reverse transcription PCR (RT-qPCR) and Western blot. Then, the cell viability, inflammatory responses, oxidative stress and apoptosis were detected by CCK-8, enzyme linked immunosorbent assay (ELISA), oxidative stress detection kits, and TdT-mediated dUTP Nick-End Labeling (TUNEL) respectively. Inflammation- and apoptosis-related markers were also measured by Western blot. The cell viability reduced by LPS in BEAS2B cells was elevated by carvedilol. Moreover, RhoA/ROCK were found to be suppressed by carvedilol administration. The cell viability, inflammation, oxidative stress and apoptosis of LPS-induced BEAS2B cells were aggravated upon RhoA was overexpressed. Collectively, carvedilol exerts a protective effect against LPS-induced injury that could be ascribed to its anti-inflammatory and antioxidative character through modulating the RhoA/ROCK activities.
卡维地洛具有抗氧化和神经保护等多种功能，RhoA/ROCK 已被报道参与急性肺损伤（ALI）。本研究旨在探讨卡维地洛在 LPS 诱导的 ALI 中的作用。采用 LPS 构建 BEAS2B 细胞体外 ALI 模型，通过细胞计数试剂盒（CCK-8）评估卡维地洛的保护作用。然后通过实时定量 RT-PCR（RT-qPCR）和 Western blot 测定 RhoA/ROCK 的活性，以确认其与卡维地洛的关联。然后通过 CCK-8、酶联免疫吸附试验（ELISA）、氧化应激检测试剂盒和末端转移酶介导的 dUTP 缺口末端标记（TUNEL）分别检测细胞活力、炎症反应、氧化应激和细胞凋亡。通过 Western blot 还测定了炎症和细胞凋亡相关标志物。LPS 可降低 BEAS2B 细胞的活力，而卡维地洛可提高其活力。此外，卡维地洛可抑制 RhoA/ROCK 的表达。RhoA 过表达可加重 LPS 诱导的 BEAS2B 细胞活力、炎症、氧化应激和细胞凋亡。综上所述，卡维地洛通过调节 RhoA/ROCK 的活性发挥对 LPS 诱导损伤的保护作用，其具有抗炎和抗氧化作用。
