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.