Atorvastatin decreased the contrast-induced renal tubular epithelial cell apoptosis through regulation of the PERK/eIF2α/CHOP signaling pathway

Abstract

Objective To investigate the expression of glucose regulated protein 78 (GRP78), protein kinase R-like ER kinase (PERK), eukaryotic initiation factor 2α (eIF2α), and C/EBP homologous protein (CHOP), in order to evaluate the effect of endoplasmic reticulum stress in rats with contrast induced-acute kidney injury (CI-AKI), and observe the possible protective effect of atorvastatin in CI-AKI rats. Methods Sixty Wistar rats were randomly divided into control group, CI-AKI model group, high-dose atorvastatin group (80 mg), and low-dose atorvastatin group (40 mg) with 15 rats each. At 24 h, 48 h, and 72 h after the rat model was established, BUN and Scr were detected. TUNEL and Western blotting were used to detect the apoptosis of renal tubular epithelial cells and caspase-3 expression, respectively. Immunohistochemistry and Western blotting were used to detect the expression of GRP78, p-eIF2α, p-PERK, and CHOP in the rat renal tissues. Results Compared with the control group, the model group had higher levels of BUN and Scr, more apoptotic cells, and more expression of GRP78, p-eIF2α, p-PERK, and CHOP (P<0.05). Both the high- and low-dose atorvastatin groups had lower levels of BUN and Scr, fewer apoptotic cells, and less expression of GRP78, p-eIF2α, p-PERK, and CHOP than the model group, which were yet higher than those of the control group (P<0.05). The differences of the levels of BUN, Scr, apoptosis of tubular cells, and expression of GRP78, p-eIF2α, p-PERK and CHOP proteins were not significant between the high-dose and low-dose atorvastatin groups. Conclusion Endoplasmic reticulum stress mediated by the PERK/eIF2α/CHOP pathway may be involved in the development of contrast- enhanced nephropathy in rats. Atorvastatin may play a protective role in contrast-induced renal injury by its regulation of the PERK/eIF2α/CHOP pathway leading to reduced endoplasmic reticulum stress. Key words: Contrast medium; Endoplasmic reticulum stress; Glucose-regulated protein 78; Atorvastatin