Guo Yan, Lu Miao, Qian Jin, Cheng Yun-lin
Department of Gerontology, First Affiliated Hospital to Nanjing Medical University, China.
J Gerontol A Biol Sci Med Sci. 2009 Jun;64(6):629-35. doi: 10.1093/gerona/glp023. Epub 2009 Mar 18.
To investigate the possible effects of alagebrium chloride (ALT-711) on oxidative stress (OS) process in aging hearts, we examined the role of ALT-711 in cardiac function and OS in the heart of aging rats. Increased mitochondrial DNA (mtDNA) deletion as well as nearly a twofold increase in advanced glycation end products (AGEs) accumulation were observed in aging heart, whereas only about 50% of the superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were seen. However, after treatment with ALT-711, preserved cardiac diastolic function accompanied with reduced mtDNA deletion and about 30% of AGEs decrease was observed in aging hearts. In addition, ALT-711 can increase SOD and GSH-PX activities in aging hearts as well as in cultured cardiomyocytes. In conclusion, our study suggests that AGEs accumulation and the abnormalities in the OS in aging hearts can be attenuated by ALT-711, and this might be a novel underlying mechanism for ALT-711 in the treatment of cardiovascular diseases that develop with aging.
为研究氯化氨基胍（ALT-711）对衰老心脏氧化应激（OS）过程的可能影响，我们检测了ALT-711在衰老大鼠心脏功能及OS中的作用。在衰老心脏中观察到线粒体DNA（mtDNA）缺失增加以及晚期糖基化终产物（AGEs）积累增加近两倍，而超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）活性仅约为正常的50%。然而，用ALT-711治疗后，衰老心脏的心脏舒张功能得以保留，同时mtDNA缺失减少，AGEs减少约30%。此外，ALT-711可增加衰老心脏以及培养心肌细胞中的SOD和GSH-PX活性。总之，我们的研究表明，ALT-711可减轻衰老心脏中AGEs的积累和OS异常，这可能是ALT-711治疗随衰老发生的心血管疾病的一种新的潜在机制。
