Study on mTOR pathway in rats with diabetic nephropathy podocyte injury

ZHONG Mei-fang; ZHAO Qing; LI Qiu-yue; CHEN Qin-kai

doi:10.3969/j.issn.1001-9448.2017.23.004

Abstract：Objective To observe effects of mTOR blocker on podocyte protein in diabetic nephropathy ( DN) rats, and to investigate the potential mechanism of DN podocyte injury .Methods Normal rats as control group ( A group).The DN rat models were induced with STZ method , and randomly divided into DN group ( B group), DN +FK506 group (C group) and DN+ku0063794 group (D group).FK506 and ku0063794 were given to rats in C group and D group, respectively.The blood glucose, creatinine clearance rate (Ccr), 24-hour proteinruia, mTOR, Raptor, Ric-tor, Ezrin and α-SMA protein at the 0, 4 and 8 weeks were measured .Results The 24-hour proteinruia in B groups were significantly higher than A group ( P<0.05 ) .The Ccr in B groups were significantly lower than A group ( P<0.05).The mTOR in B groups were significantly higher than A group (P<0.05), while it was significantly lower in C、D groups than B group (P<0.05).Raptor and Rictor proteins in B groups were significantly higher than A group (P<0.05), while they were significantly lower in C、D groups than B group (P<0.05).Ezrin in B groups were significantly lower than A group (P<0.05), while it was significantly higher in C、D groups than B group (P<0.05).α-SMA in B group was significantly higher than A group (P<0.05), while it was significantly lower in C、 D groups than B group (P<0.05).Pathological scores in C、 D groups were significantly reduced when compared with B group (P<0.05). Rictor was significantly positively correlated with α-SMA and negatively correlated with Ezrin .However , there was no significant correlation between Raptor and Ezrin or α-SMA.Conclusion The mTORC2 pathways may participate in the expression of podocyte Ezrin and α-SMA proteins in DN , and FK506 may also block mTORC2 signaling pathways .