Inhibition of ALDH2 expression aggravates renal injury in a rat sepsis syndrome model.

Abstract

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is closely associated with organ injury. The aim of the present study was to investigate the change of ALDH2 expression in a rat model of sepsis-induced acute renal injury, and to observe the effect of ALDH2 inhibition on the kidney. A model of sepsis syndrome was established in Sprague-Dawley (SD) rats by cecal ligation and puncture (CLP). The rats were divided into sham, CLP and CLP + cyanamide (CYA, an ALDH2 inhibitor) groups. The hemodynamic parameters heart rate (HR) and mean arterial blood pressure (MABP) were measured. Plasma creatinine (CRE) and urea nitrogen (BUN) levels were measured using an automatic biochemical analyzer. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the kidney tissue were measured. Histological changes of the kidney tissue were observed using hematoxylin and eosin staining and NF-κB p65 expression was observed by an immunohistochemical staining method. The expression of renal ALDH2 at the mRNA and protein levels was detected by reverse transcription-polymerase chain reaction and western blotting. In the CLP compared with the sham group after 24 h, the MABP was decreased, plasma CRE and BUN levels were elevated, the renal MDA level was increased and SOD activity was decreased. In addition, glomerular atrophy occurred, the renal protein expression of NF-κB p65 was increased, and the mRNA and protein expression levels of ALDH2 were decreased. In contrast with the CLP group, in the CLP + CYA group, the MABP and ALDH2 expression were further decreased while glomerular atrophy was aggravated. Furthermore, CRE, BUN, MDA levels and NF-κB p65 expression were further increased and SOD activity was further reduced. In this rat model of sepsis syndrome, the reduction of renal ALDH2 expression was accompanied by kidney injury. Inhibition of ALDH2 with CYA aggravated the renal injury, and was associated with the overproduction of reactive oxygen species and inflammatory reaction.