SIRT1活化对TGF-β1诱导的足细胞ILK PCNA的影响

目的探讨沉默信息调控因子1（SIRT1）活化对转化生长因子-β1（TGF-β1）诱导的肾小球足细胞整合素连接激酶（ILK）和增殖细胞核蛋白（PCNA）的影响。方法体外分化条件下培养小鼠足细胞2周，用TGF-β1（2ng／ml）诱导作为模型组，分别加白藜芦醇（5μM）和不同浓度的SRT1720（2μM、1μM）进行干预。以CCK-8检测细胞存活率，通过Western Blot技术检测ILK、PCNA和α-平滑肌肌动蛋白（α-SMA）的表达。结果白藜芦醇和SRT1720对正常培养的肾小球足细胞存活率无显著影响；与正常组比较，模型组ILK、PCNA和α-SMA蛋白表达升高（P〈0．05），而经白藜芦醇和SRT1720干预后，ILK、PCNA和α-SMA蛋白表达较模型组显著降低（P〈0．05）。结论SIRT1活化可抑制TGF-β1诱导的肾小球足细胞ILK、PCNA和α-SMA蛋白的表达，可能与其抑制肾小球足细胞表型转分化，保护肾小球滤过屏障的机制有关。

Objective To explore the effect of the silent information regulator 1 （ SIRT1 ） activation on integrin linked kinase （ ILK ） and proliferating celt nuclear protein （ PCNA ） in podocyte induced by TGF- β1. Methods The mouse glomerular podocytes were cultured under differentiating conditions for 2 weeks in vitro. The podocytes incubated with TGF-β1 （ 2ng/ml ） were served as research model, and they were treated with resveratrol （ 5 μM ） or different concentration of SRT1720 （ 2 μM or 1 μM ） , respectively. The cell viability was detected by Cell Counting Kit-8 （ CCK-8 ） and the expressions of ILK, PCNA and α-SMA were detected by western blotting. Results The resveratrol and SRT1720 had no significant effect on survival rate of the normal podocyte. Compared with the control group, the expressions of ILK, PCNA and α-SMA protein increased signiificantly in the model group （P〈0.05） . However, their expressions were obviously lower in the resveratrol and SRT1720 intervention groups than that in the model group （P〈0.05） . Conclusion The activation of SIRT1 can inhibit the expression of ILK, PCNA and α-SMA in glomerular podocytes induced by TGF-β1, which may be related to the mechanism of inhibiting the phenotypic trans-differentiation of glomerular podocytes and protecting the glomerular filtration battier.