To investigate the role of AT₁ receptor autoantibody(AT₁-AA)in the inhibitory action of irbesartan on endoplasmic reticulum stress(ERS)-related apoptotic signals in rat kidney with diabetic nephropathy(DN).

DN model rats were induced by high-sugar and high-fat diet plus intraperitoneal injection of streptozotocin, and the serum level of AT₁-AA was detected by ELISA. These DN rats with positive or negative AT₁-AA were divided into DN group and irbesartan treated group. After 4 weeks of irbesartan treatment, TUNEL staining was used to detect renal cell apoptosis. The protein and mRNA expressions of ERS chaperone protein glucose-regulated protein 78(GRP78)and ERS-associated apoptosis proteins were determined by Western blot and RT-PCR.

Compared with NC group, the apoptosis rate of renal cells in DN group was obviously increased, along with the increased expressions of GRP78, C/EBP homology protein(CHOP), phosphorylated c-Jun N-terminal kinase(JNK), and Caspase12 protein and mRNA(all P<0.01). The cell apoptosis and protein and mRNA levels of these genes were significantly decreased after irbesartan treatment(all P<0.01), especially in AT₁-AA positive DN rats(all P<0.05). The renal cell apoptosis rate, and protein and mRNA levels of these four genes in AT₁-AA positive DN group were much greater than those in AT₁-AA negative DN group(all P<0.05).

AT₁-AA may be involved in ERS-related cell apoptosis in the kidney of DN rats, and play a role in irbesartan-improved renal function via inhibiting ERS-associated CHOP-JNK-Caspase12 apoptotic signals and renal cell apoptosis. (Chin J Endocrinol Metab, 2015, 31: 400-405)

AT₁ receptor autoantibody; Irbesartan; Endoplasmic reticulum stress; Apoptosis; Diabetic nephropathy