醋酸盐，一种肠道细菌产物，可改善大鼠缺血再灌注引起的急性肺损伤。
Acetate, a gut bacterial product, ameliorates ischemia-reperfusion induced acute lung injury in rats.
机构信息
The Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan.
出版信息
Int Immunopharmacol. 2022 Oct;111:109136. doi: 10.1016/j.intimp.2022.109136. Epub 2022 Aug 11.
Recent data suggest that short-chain fatty acids (SCFAs), the major fermentation product from gut microbial degradation of dietary fiber, have protective effects against renal ischemia-reperfusion (IR) injury, colitis, and allergic asthma. However, the effect of SCFAs on acute lung injury (ALI) caused by IR is still unclear. In this study, we examine whether SCFAs have protective effects against IR-induced ALI and explore possible protective mechanisms. IR-induced ALI was established by 40 min ischemia followed by 60 min reperfusion in isolated perfused rat lungs. Rats were randomly assigned to one of six groups: control, control + acetate (400 mg/kg), IR, and IR + acetate at one of three dosages (100, 200, 400 mg/kg). Bronchoalveolar lavage fluids (BALF) and lung tissues were obtained and analyzed at the end of the experiment. In vitro, mouse lung epithelial cells (MLE-12) subjected to hypoxia-reoxygenation (HR) were pretreated with acetate (25 mmol/L) and GPR41 or GPR43 siRNA. Acetate decreased lung weight gain, lung weight/body weight ratios, wet/dry weight ratios, pulmonary artery pressure, and protein concentration of the BALF in a dose-dependent manner for IR-induced ALI. Acetate also significantly inhibited the production of TNF-α, IL-6 and CINC-1 in the BALF. Moreover, acetate treatment restored suppressed IκB-α levels and reduced nuclear NF-κB p65 levels in lung tissues. In addition, acetate mitigated IR-induced apoptosis and tight junction disruption in injured lung tissue. In vitro analyses showed that acetate attenuated NF-κB activation and KC/CXCL-1 levels in MLE-12 cells exposed to HR. The protective effects of acetate in vitro were significantly abrogated by GPR41 or GPR43 siRNA. Acetate ameliorates IR-induced acute lung inflammation and its protective mechanism appears to be via the GPR41/43 signaling pathway. Based on our findings, acetate may provide a novel adjuvant therapeutic approach for IR-induced lung injury.
最近的数据表明，短链脂肪酸（SCFAs）是肠道微生物降解膳食纤维的主要发酵产物，对肾缺血再灌注（IR）损伤、结肠炎和过敏性哮喘具有保护作用。然而，SCFAs 对 IR 引起的急性肺损伤（ALI）的影响尚不清楚。在这项研究中，我们研究了 SCFAs 是否对 IR 诱导的 ALI 具有保护作用，并探讨了可能的保护机制。通过在分离灌注的大鼠肺中缺血 40 分钟后再灌注 60 分钟来建立 IR 诱导的 ALI。大鼠被随机分为六组之一：对照组、对照组+醋酸盐（400mg/kg）、IR 组和 IR 组+醋酸盐（100、200、400mg/kg）的三个剂量组之一。在实验结束时，获得支气管肺泡灌洗液（BALF）和肺组织并进行分析。在体外，用醋酸盐（25mmol/L）和 GPR41 或 GPR43 siRNA 预处理缺氧-复氧（HR）的小鼠肺上皮细胞（MLE-12）。醋酸盐以剂量依赖性方式降低 IR 诱导的 ALI 时的肺重增加、肺重/体重比、湿/干重比、肺动脉压和 BALF 中蛋白浓度。醋酸盐还显著抑制了 BALF 中 TNF-α、IL-6 和 CINC-1 的产生。此外，醋酸盐处理恢复了肺组织中抑制的 IκB-α 水平并降低了核 NF-κB p65 水平。此外，醋酸盐减轻了损伤肺组织中 IR 诱导的细胞凋亡和紧密连接破坏。体外分析表明，醋酸盐减弱了 HR 暴露的 MLE-12 细胞中 NF-κB 的激活和 KC/CXCL-1 水平。GPR41 或 GPR43 siRNA 显著削弱了醋酸盐在体外的保护作用。醋酸盐改善了 IR 诱导的急性肺炎症，其保护机制似乎是通过 GPR41/43 信号通路。基于我们的发现，醋酸盐可能为 IR 诱导的肺损伤提供一种新的辅助治疗方法。
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