Lisinopril suppresses the endoplasmic reticulum stress associated tubular cell apoptosis induced by proteinuria in adriamycin nephropathy

Objective To investigate the role of endoplasmic reticulum stress in tubular epithelial cell apoptosis in chronic proteinuria rat model and the effect of lisinopril intervention. Methods Adriamycin nephropathy was induced in male Wistar rats (n=12) by a single injection of adriamycin at 2 mg/kg body weight. Rats were then randomly assigned to model group or treatment group, to which distilled water or lisinopril were administered respectively for 12 weeks. Six normal rats serving as controls were administered distilled water. 24 h urine samples were collected at week 4, 8, 12 and the urine protein was measured. At the end of study, serum was obtained and physiological parameters (serum creatinine, urea, total protein and albumin) were measured. Renal tubular epithelial cell apoptosis was assessed by TUNEL. GRP78, CHOP protein expression in kidney was quantified by immunohistochemistry and Western blotting. Results Compared to control group rats, increased proteinuria was observed in model group rats at week 4, 8, 12 (P 0.05). Compared to control group rats, increased TUNEL positive tubular epithelial cells and tubular GRP78 and CHOP expression were also observed in model group rats (P <0.05); however, these conditions in the kidney were significantly decreased in treatment group (P <0.05). Conclusions Endoplasmic reticulum stress may be involved in the process of tubular epithelial cell apoptosis induced by proteinuria. Lisinopril may attenuate tubular epithelial cell apoptosis through regulating this signal pathway. Key words: Lisinopril; Proteinuria; Apoptosis; Endoplasmic reticulum stress; Tubular epithelial cells