盐酸右美托咪定对2-氯乙基乙基硫醚致人支气管上皮细胞损伤的保护作用及机制

doi:10.3969/j.issn.1004-616x.2024.05.002

Abstract

Abstract: OBJECTIVE： To investigate protective effect and mechanism of dexmedetomidine hydrochloride (DEX) on blister agent 2-chloroethyl ethyl sulfide (CEES)-induced injury in human bronchial epithelial cells. METHODS： BEAS-2B cells were exposed to 1.2 mmol/L CEES for 24 h to establish a cell damage model induced by blister agents. The cells were pretreated with various concentrations of DEX for 2 h and exposed to CEES for 24 h. Cell viability was detected by the CCK-8 method to determine the optimal protective dose of DEX. Cell morphology was observed under a light microscope，and cell apoptosis rates were measured using Annexin V/PI staining. DHE，MitoSOX and RHOD123 fluorescent probes were employed to detect total reactive oxygen species (ROS)，mitochondrial ROS (mtROS) and mitochondrial membrane potential levels，respectively. Enzyme activities of total SOD，CuZn-SOD and Mn-SOD and content of GSH were detected by kits. RESULTS： Compared with the control group，the CEES group showed a significant decrease in cell viability (P<0.01)，a significant increase in cell apoptosis (P<0.01)，a significant increase in ROS and mtROS (P<0.01)，a significant decrease in mitochondrial membrane potential (P<0.01)，an increase in total SOD，CuZn-SOD and Mn-SOD enzyme activity (P<0.01)，and a decrease in GSH content (P<0.01). Compared with the CEES group，the cell viability of 0.1-1 000 μmol/L DEX intervention group was increased，and the most significant increase in cell viability was observed in the 10 μmol/L DEX intervention group (P<0.01)，and 10 μmol/L was used as the optimal dose for the follow DEX intervention group. Apoptosis was decreased after the 10 μmol/L DEX intervention (P<0.01). Compared with the CEES treatment group，DEX intervention reduced mtROS (P<0.01)，increased mitochondrial membrane potential (P<0.05)，increased enzyme activity of total SOD and CuZn-SOD (P<0.01)，and increased GSH content (P<0.01). CONCLUSION： DEX exerted a protective effect on CEES-induced injury in human bronchial epithelial cells，and its mechanism could be related to the regulation of mitochondrial homeostasis，the reduction of mtROS production and the enhancement of cellular antioxidant levels.

Key words: blister agents, dexmedetomidine hydrochloride, mitochondria, oxidative stress, reactive oxygen species

CLC Number:

R858.5

SHI Minjie, LI Jia, DENG Zifeng, ZHAN Tianhao, LIU Jianhao, ZHAO Yushun, LI Wenli, LIU Jiangzheng, KONG Deqin. Mechanism of dexmedetomidine hydrochloride on 2-chloroethyl ethyl sulfide-induced injury in human bronchial epithelial cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2024, 36(5): 342-348,358.

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Mechanism of dexmedetomidine hydrochloride on 2-chloroethyl ethyl sulfide-induced injury in human bronchial epithelial cells

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