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目的:探讨晚期糖基化终产物(AGEs)诱导心肌成纤维细胞老化及纤维化的相关机制。方法:用AGEs(200μg/ml)及抗RAGE抗体(2μg/ml)、TGF-β1/smad通路抑制剂(SB431542,10μmol/L)干预乳鼠心肌成纤维细胞72 h。观察老化相关指标β-半乳糖苷酶的活性及p16的表达;Western blot检测TGF-β1、p-smad2/3、MMP-2的水平。结果:AGEs干预72 h后,AGEs组细胞老化指标β-半乳糖苷酶的活性及p16的表达水平较对照组明显升高(P<0.01),伴有TGF-β1、p-smad2/3、MMP-2水平的显著增高,而给予抗RAGE抗体或SB431542干预后,β-半乳糖苷酶的活性及p16的表达水平较AGEs组明显下降,同时TGF-β1、p-smad2/3、MMP-2的水平也显著下降。结论:推测AGEs可与其受体RAGE作用诱导心肌成纤维细胞的老化,而TGF-β1/smad信号通路引发的心肌纤维化可能参与了这一过程。
Objective: To investigate the mechanism of advanced glycation end products (AGEs) inducing myocardial fibroblasts aging and fibrosis. Methods: The neonatal rat cardiac fibroblasts were treated with AGEs (200μg / ml), anti-RAGE antibody (2μg / ml) and TGF-β1 / smad pathway inhibitor (SB431542,10μmol / L) for 72 hours. The activity of β-galactosidase and the expression of p16 were observed. The levels of TGF-β1, p-smad2 / 3 and MMP-2 were detected by Western blot. Results: After AGEs were administered for 72 h, the activity of β-galactosidase and the expression of p16 in AGEs group were significantly higher than those in control group (P <0.01), and the expressions of TGF-β1, p-smad2 / Β1, p-smad2 / 3, MMP-2 levels were significantly increased, while the anti-RAGE antibody or SB431542 intervention, β-galactosidase activity and p16 expression levels were significantly decreased compared with AGEs group, 2 levels also dropped significantly. CONCLUSIONS: It is speculated that AGEs may induce cardiomyocyte fibroblasts aging with its receptor RAGE, and that fibrosis induced by TGF-β1 / smad signaling pathway may be involved in this process.