晚期糖基化终产物对心肌成纤维细胞的老化及纤维化的影响
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江苏省科技厅自然科学基金(BK2011382),江苏省“六大人才高峰”(2011WSN-029),江苏省卫生厅科技项目(Z201301)


Aging and fibrosis effects of advanced glycation end products on cardiac fibroblasts
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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(200 μg/ml)及抗RAGE抗体(2 μg/ml)-TGF-β1/smad通路抑制剂(SB431542,10 μmol/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-

    Abstract:

    Objective:To investigate the mechanisms of cardiac fibroblasts aging and fibrosis induced by advanced glycosylation end-productcs(AGEs). Methods:Neonatal rat cardiac fibroblasts were incubated for 72h with AGEs(200 μg/ml),anti-RAGE antibody (2 μg/ml) and TGFβ/smad signaling pathway inhibitor (SB431542,10 μmol/L). Senescence-associated beta galactosidase activity and p16 expression were observed;MMP-2,TGF-β1 and p-smad2/3 were measured by Western blot. Results:After intervened with AGEs for 72 h,senescence-associated beta galactosidase activity and the level of p16 in the AGEs group were significantly increased compared with the control group(P < 0.01),accompanied with significant increases of the expressions of TGF-β1,p-smad2/3 and MMP-2. However,senescence-associated beta galactosidase activity and the expression of p16 were remarkably down-regulated after the pretreatment of anti-RAGE antibody and SB431542 compared with those of the AGEs group,meanwhile,the levels of TGF-β1,p-smad2/3 and MMP-2 were also significantly decreased. Conclusion:We conclude that AGEs could induce cardiac fibroblasts aging through binding to its receptor RAGE,and cardiac fibrosis induced by TGF-β/smad pathway could be involved in this process.

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方 敏,李世玲,王俊宏,郭 妍.晚期糖基化终产物对心肌成纤维细胞的老化及纤维化的影响[J].南京医科大学学报(自然科学版),2014,(1):022-026

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  • 收稿日期:2013-06-27
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  • 在线发布日期: 2014-01-27
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