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  

Aging and fibrosis effects of advanced glycation end products on cardiac fibroblasts

作　　者：方敏 李世玲 王俊宏 郭妍 

机构地区：[1]南京医科大学第一附属医院老年心血管科,江苏南京210029 [2]江苏盛泽医院心血管科,江苏苏州215228

出　　处：《南京医科大学学报（自然科学版）》2014年第1期22-26,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：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)

摘　　要：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 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.

关 键 词：AGES RAGE TGF-β SMAD 心肌老化 心肌纤维化 

分 类 号：R587.2[医药卫生—内分泌]