背景:慢性阻塞性肺疾病(COPD)中存在细胞因子风暴和氧化应激。患有COPD的个体呈现高水平的NF-κB相关的细胞因子和促氧化剂以及低水平的Nrf2相关的抗氧化剂。这种情况产生类固醇抗性的炎症微环境。鼠李糖乳杆菌(Lr)是肺部疾病中已知的抗细胞因子;然而,Lr对类固醇耐药COPD小鼠肺部炎症和氧化应激的影响尚不清楚.
目标:因此,我们研究了Lr对暴露于香烟烟雾提取物(CSE)且对类固醇无反应的小鼠和巨噬细胞的肺部炎症和氧化应激的影响。
方法:小鼠和巨噬细胞接受地塞米松或GLPG-094(GPR43抑制剂),只有巨噬细胞接受丁酸(但是),在CSE之前给予所有治疗。从白细胞群体评估肺部炎症,气道重塑,细胞因子,和NF-κB。从ROS测量氧化应激紊乱,8-异前列腺素,NADPH氧化酶,TBARS,SOD,过氧化氢酶,HO-1和Nrf2。
结果:Lr减弱了细胞数量,粘液,胶原蛋白,细胞因子,ROS,8-异前列腺素,NADPH氧化酶,TBARS否则,SOD,过氧化氢酶,HO-1和Nrf2在Lr处理的COPD小鼠中上调。丁酸盐的抗细胞因子和抗氧化作用也发生在CSE暴露的巨噬细胞中。GLPG-094使得Lr和丁酸盐效果较差。
结论:Lr减轻COPD小鼠的肺部炎症和氧化应激,这表明在巨噬细胞中也存在GPR43受体依赖性机制。
BACKGROUND: Cytokine storm and oxidative stress are present in chronic obstructive pulmonary disease (COPD). Individuals with COPD present high levels of NF-κB-associated cytokines and pro-oxidant agents as well as low levels of Nrf2-associated antioxidants. This condition creates a steroid-resistant inflammatory microenvironment. Lacticaseibacillus rhamnosus (Lr) is a known anti-cytokine in lung diseases; however, the effect of Lr on lung inflammation and oxidative stress in steroid-resistant COPD mice remains unknown.
OBJECTIVE: Thus, we investigated the Lr effect on lung inflammation and oxidative stress in mice and macrophages exposed to cigarette smoke extract (CSE) and unresponsive to steroids.
METHODS: Mice and macrophages received dexamethasone or GLPG-094 (a GPR43 inhibitor), and only the macrophages received butyrate (but), all treatments being given before CSE. Lung inflammation was evaluated from the leukocyte population, airway remodeling, cytokines, and NF-κB. Oxidative stress disturbance was measured from ROS, 8-isoprostane, NADPH oxidase, TBARS, SOD, catalase, HO-1, and Nrf2.
RESULTS: Lr attenuated cellularity, mucus, collagen, cytokines, ROS, 8-isoprostane, NADPH oxidase, and TBARS. Otherwise, SOD, catalase, HO-1, and Nrf2 were upregulated in Lr-treated COPD mice. Anti-cytokine and antioxidant effects of butyrate also occurred in CSE-exposed macrophages. GLPG-094 rendered Lr and butyrate less effective.
CONCLUSIONS: Lr attenuates lung inflammation and oxidative stress in COPD mice, suggesting the presence of a GPR43 receptor-dependent mechanism also found in macrophages.