Yu Fenfang, Ma Jiyong, Xu Ke, Tang Yu, Wu Bining, Gu Wei, Shi Ying
Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Department of Respiratory Medicine, Nanjing Yuhua Hospital, Yuhua Branch of Nanjing First Hospital, Nanjing, China.
J Thorac Dis. 2024 Aug 31;16(8):5005-5017. doi: 10.21037/jtd-23-1820. Epub 2024 Aug 14.
The current clinical treatment of chronic obstructive pulmonary disease (COPD) mainly uses drugs to improve symptoms, but these drugs cannot reverse the progression of the disease and the pathological changes in lung tissue. This study aimed to investigate the effects and mechanisms of Liver X receptors (LXRs) in ozone (O3)-induced airway inflammation and remodeling in mice.
Wild mice and LXR deficient mice were exposed to O3 twice a week for 6 weeks. Some wild mice were intraperitoneally injected with T0901317 (a LXR agonist) before O3 exposure. Wild mice were exposed to ambient air and intraperitoneally injected with normal saline (NS) as control group. The lung tissues and bronchoalveolar lavage fluid (BALF) were collected to evaluate airway inflammation, airway remodeling and lipid disorder.
After O3 exposure, LXR deficient mice showed severe airway inflammation and airway remodeling compared with the wild mice. There were a lot of foamy macrophages appeared in BALF of LXR deficient mice. The inflammatory proteins such as myeloid differentiation primary response protein 88 (MyD88) and interleukin-1 receptor-associated kinase (IRAK) in the lung tissues of LXR deficient mice were significantly increased compared with the wild mice. In wild mice exposed to O3, T0901317 treatment can alleviate airway inflammation, airway remodeling and foamy macrophages in BALF. And MyD88 and IRAK expression in lung tissue were also attenuated by T0901317 treatment.
LXRs play protective roles in O3-induced lipid accumulation, airway inflammation and airway remodeling.
慢性阻塞性肺疾病（COPD）目前的临床治疗主要使用药物来改善症状，但这些药物无法逆转疾病进展和肺组织的病理变化。本研究旨在探讨肝脏X受体（LXRs）在臭氧（O3）诱导的小鼠气道炎症和重塑中的作用及机制。
将野生型小鼠和LXR基因敲除小鼠每周暴露于O3两次，持续6周。部分野生型小鼠在暴露于O3之前腹腔注射T0901317（一种LXR激动剂）。将暴露于环境空气并腹腔注射生理盐水（NS）的野生型小鼠作为对照组。收集肺组织和支气管肺泡灌洗液（BALF）以评估气道炎症、气道重塑和脂质紊乱。
与野生型小鼠相比，O3暴露后，LXR基因敲除小鼠表现出严重的气道炎症和气道重塑。LXR基因敲除小鼠的BALF中出现大量泡沫巨噬细胞。与野生型小鼠相比，LXR基因敲除小鼠肺组织中的炎症蛋白如髓样分化初级反应蛋白88（MyD88）和白细胞介素-1受体相关激酶（IRAK）显著增加。在暴露于O3 的野生型小鼠中，T0901317治疗可减轻气道炎症、气道重塑和BALF中的泡沫巨噬细胞。T0901317治疗还可使肺组织中MyD88和IRAK的表达减弱。
LXRs在O3诱导的脂质蓄积、气道炎症和气道重塑中发挥保护作用。
