The role of programmed cell death in streptozotocin-induced early diabetic nephropathy.

The mechanism of autophagy in diabetic nephropathy (DN) is still unclear. The study was performed on streptozotocin (STZ) rats to investigate whether programmed cell death contribute to the pathogenesis and progression of DN. STZ rats were induced by an single intravenous injection of STZ dissolved in citrate buffer, early DN (E-DN) for STZ rats was defined as the stage from modeling to the end of the 8th week according to previous studies. A total of 36 male Sprague-Dawley rats were randomly divided into two groups: an E-DN group and a control group. After the 1st, 4th, and 8th week, the rats were sacrificed. Beclin1 and microtubule associated protein 1 light chain 3 (LC3) were examined, apoptosis level in renal tissue was detected by Tunnel assay detected as the apoptotic index. An electron microscopic examination of kidney tissues was performed at end of the 4th and 8th week. Compared with the control group, Beclin1 expression increased since the 1st week after modeling in STZ rats kidney and peaked at the end of the 8th week in western blotting and immunohistochemical stain. Meanwhile the level of LC3-II in DN group was significantly lower from the end of the 1st to the 8th week. A small amount of autophagosomes were observed in both E-DN group and control group under electron microscopic examination, and there was no significant difference between the groups. These findings indicate that an abnormality on autophagy may play an important role in the pathogenesis of E-DN.