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该文研究了白藜芦醇及其下游信号分子沉默信息调节因子1(silent information regulator 1,SIRT1)对高糖培养条件下人肾小管上皮细胞(HK-2)转化的作用和机制。体外常规培养HK-2细胞,采用Western blot检测平滑肌肌动蛋白(α-SMA)、E-钙黏着蛋白(E-cadherin)及信号蛋白SIRT1、过氧化物酶体增殖物激活受体γ协同刺激因子-1α(peroxisome proliferator-activated receptor gamma coactivator-1α,PGC-1α)的蛋白表达,采用细胞免疫荧光对SIRT1的表达进行检测。与高糖刺激0 h组相比,高糖刺激12,24,48 h均导致HK-2细胞SIRT1蛋白明显减少,且随时间呈下降趋势;低糖培养细胞0,12,24,48 h的SIRT1蛋白表达没有明显差异。白藜芦醇明显提高高糖培养条件下HK-2细胞的SIRT1表达,而SIRT1特异性抑制剂EX527能够减弱白藜芦醇的作用。进一步的研究表明,白藜芦醇能够明显增加HK-2细胞中E-钙黏着蛋白的表达,抑制高糖导致的α-SMA表达升高,而EX527对高糖诱导的HK-2细胞转分化没有显著影响。此外,研究发现,白藜芦醇能够明显增加高糖刺激下HK-2细胞PGC-1α蛋白表达。该研究结果提示,白藜芦醇可能通过SIRT1和PGC-1α信号通路抑制了高糖诱导的HK-2细胞转化过程。
In this paper, we investigated the effect and mechanism of resveratrol and its downstream signaling molecule silent information regulator 1 (SIRT1) on the transformation of human renal tubular epithelial cells (HK-2) under high glucose conditions. HK-2 cells were cultured in vitro. The expressions of α-SMA, E-cadherin, SIRT1 and peroxisome proliferator-activated receptor γ were measured by Western blot. Protein expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), the expression of SIRT1 was detected by immunofluorescence. Compared with the high glucose group, the SIRT1 protein in HK-2 cells decreased significantly at 12, 24 and 48 h after high glucose stimulation, and decreased with the increase of time. SIRT1 at 0, 12, 24 and 48 h There was no significant difference in protein expression. Resveratrol significantly increased SIRT1 expression in HK-2 cells under high glucose conditions, whereas SIRT1-specific inhibitor EX527 attenuated the effects of resveratrol. Further studies showed that resveratrol significantly increased the expression of E-cadherin in HK-2 cells and inhibited the elevated α-SMA expression induced by high glucose, while EX527 inhibited the transdifferentiation of HK-2 cells induced by high glucose No significant effect. In addition, the study found that resveratrol significantly increased the PGC-1α protein expression in HK-2 cells induced by high glucose. The results suggest that resveratrol may inhibit high glucose-induced HK-2 cell transformation through the SIRT1 and PGC-1α signaling pathways.