Role of endoplasmic reticulum stress-induced apoptosis of renal tubular epithelial cells in rhabdomyolysis-associated acute kidney injury / 解放军医学杂志

ABSTRACT

Objective To investigate whether apoptosis of renal tubular epithelial cells induced by endoplasmic reticulum stress (ERS) takes a role in the traumatic rhabdomyolysis-induced acute kidney injury (AKI). Methods The model of rhabdomyolysis-induced AKI was reproduced by intramuscular injection of hypertonic glycerol into the hind limbs in male Wistar rats. There were 11 animal groups (each n=3) including control, 1h, 3h, 6h, 12h, 24h, 48h, 72h, 96h, 120h and 168h groups. Serum and renal tissue were collected at various time points. Parameters of renal function and renal pathology were used to evaluate renal injury at various time points. The renal tubular epithelial cell apoptosis was revealed by TUNEL staining at each time point. The expressions of factors, caspase-8, cytochrome C and caspase-9 activity fragments, involved in apoptosis as induced by Fas ligand/ receptor interaction and mitochondria were determined by Western blotting at each time point. Furthermore, the expressions of endoplasmic reticulum chaperone protein GRP78 and apoptosis factor caspase-12 activity fragment were also assayed by Western blotting. Results Pathological changes of tubular epithelial cells were detected at 1h, presenting a large area of necrosis at 24h, with the highest number of apoptotic renal tubular epithelial cells. Tubular-interstitial injury reached the peak at 72h. The expression of apoptotic factors (caspase-8, cytochrome C and caspase-9) was elevated reaching the peak at 12h. The change in endoplasmic reticulum stress protein expressions of GRP-78 showed a similar trend as that of caspase-12 (increased at 1h, and reached the peak at 12h). Conclusions Apoptosis of renal tubular epithelial cell is the main pathogenesis of rhabdomyolysis-induced renal injury. In addition to the activation of the death-receptor and the mitochondrial death pathway, endoplasmic reticulum stress also plays an important role in this process.