Relationship of angiotensin Ⅱ type 1 receptor autoantibody and renal cell apoptosis induced by caspase-12 in diabetic nephropathy rats / 中华肾脏病杂志

ABSTRACT

Objective To study the relationship of angiotensin Ⅱ type 1 receptor (AT1R) autoantibody (AT1-AA) and renal cell apoptosis induced by caspase-12 in diabetic nephropathy (DN)rats.Methods High-sucrose and high-fat diet and intraperitoneal injection of streptozotocin (35 mg/kg) were utilized to establish DN rat model.Serum AT1-AA was detected by enzyme-linked immunosorbent assay (ELISA) and renal cell apoptosis was detected by TUNEL staining.Furthermore,the mRNA levels of the endoplasmic reticulum stress (ERS) chaperone protein glucose regulated protein 78 (GRP78) and ERS-associated apoptosis protein caspase-12 were measured by real-time quantitative PCR.Additionally,the levels of GRP78 and caspase-12 protein were measured by Western blotting.Results The renal cell apoptosis rate in DN group was increased significantly (P ＜ 0.01),and the renal cells apoptosis rate in AT1-AA positive DN group was higher than that in AT1-AA negative DN group [(20.05±1.71)％ vs (13.24±4.93)％,P ＜ 0.01].The mRNA expressions of GRP78 and caspase-12 in DN group,in comparison to NC group,were increased significantly (P ＜ 0.01),as well as the proteins (P ＜ 0.01).And the expression of these mRNA and proteins had significant increment in AT1-AA positive DN rats when compared with AT1-AA negative DN rats (P ＜ 0.05).Conclusions AT1-AA can induce ERS in the renal tissue of DN rats,and promote renal cell apoptosis likely via the modulation of caspase-12 signaling pathway.