FP471
EFFECT OF RAPAMYCIN ON EXPRESSION OF IL17 AND TLR4 IN EARLY STAGE OF DN RATS Free

Introduction and Aims: Though DN is generally considered as a non-inflammatory disease, there are increasing evidences showing that innate immune responses and inflammatory processes play important roles in the development and progression of DN. TLR4 is vigorously involved in the progress of kidney diseases in a sterile environment. The activation of IL-17 pathway produces inflammatory cytokines, appearing in various kidney diseases. The aim of this study is to investigate the expressions of Toll-like receptor 4 (TLR4) and pro-inflammation interleukin 17 (IL-17) in early stage of diabetic nephropathy (DN), and to assess the potential role of mTOR blockade on diabetic nephropathy in vivo.

Methods: In our study, rapamycin was used to cut off the function of mTOR in order to examine whether it would postpone the progression of diabetic nephropathy by reducing the accumulation of TLR4 and IL-17.

Results: The results showed, rapymycin attenuated albuminuria, and reduced glomerular hypertrophy and kidney injury. The expression of TLR4 and IL-17 were upregulated and reduced by rapamycin in early stage of DN. By Pearson correlation analysis, TLR4 and IL-17 had a similar trend and were positively related with renal functions index (24h urinary albumin, kidney/weight ratio). However, neither TLR4 nor IL-17 was associated with fasting blood sugar.

Conclusions: Taken together, our results confirm and extend the findings of previous studies, identifying the significance of mediator TLR4 and Th17 pathway in development of early stage DN, and also suggest rapamycin may be a robust therapy to postpone the progression of DN. According to our data, rapamycin has no effects on glucose.