Effect of low-dose ethanol on NLRP3 inflammasome in diabetes-induced lung injury

Exp Anim. 2021 Aug 6;70(3):364-371. doi: 10.1538/expanim.20-0123. Epub 2021 Apr 2.

Abstract

To observe the changes in NLR family pyrin domain containing 3 (NLRP3) inflammasome in a rat model of diabetes-induced lung injury, and investigate the effect of low-dose ethanol on the production of NLRP3 inflammasome. The type I diabetic mellitus (DM) rat model was established, and the rats were divided into four groups: normal control group (CON group), low-dose ethanol group (EtOH group), diabetes group (DM group) and DM+EtOH group. The rats were fed for 6 and 12 weeks, respectively. The ratio of lung wet weight/body weight (lung/body coefficient) was calculated, and the changes of pulmonary morphology and fibrosis were observed by HE and Masson staining. The changes in pulmonary ultra-structure were examined by electron microscopy. The expressions of mitochondrial acetaldehyde dehydrogenase 2 (ALDH2) and NLRP3 inflammasome key factors, NLRP3, ASC and caspase-1 proteins were detected by western blot. Compared with the CON group, the lung/body coefficient was increased (P<0.05), lung fibrosis occurred, ALDH2 protein expression was decreased, and NLRP3, ASC and caspase-1 protein expressions were increased in the DM rats (P<0.05). Compared with the DM group, the lung/body coefficient and fibrosis degree were decreased, ALDH2 protein expression was increased (P<0.05), and NLRP3, ASC and caspase-1 protein expressions were decreased in the DM+EtOH group (P<0.05). Hence, low-dose ethanol increased ALDH2 protein expression and alleviated diabetes-induced lung injury by inhibiting the production of NLRP3 inflammasome.

Keywords: NLRP3 inflammasome; diabetic rat; low-dose ethanol; lung injury; mitochondrial acetaldehyde dehydrogenase 2.

MeSH terms

  • Aldehyde Dehydrogenase, Mitochondrial / metabolism
  • Animals
  • Diabetes Complications / chemically induced
  • Diabetes Complications / physiopathology*
  • Dose-Response Relationship, Drug
  • Ethanol / adverse effects*
  • Inflammasomes / genetics*
  • Inflammasomes / metabolism
  • Inflammation / chemically induced
  • Inflammation / genetics
  • Lung Injury / chemically induced
  • Lung Injury / physiopathology*
  • Male
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • Ethanol
  • Aldehyde Dehydrogenase, Mitochondrial
  • Aldh2 protein, rat