多胺代谢与自噬在增龄大鼠心脏中的变化及外源性精脒对衰老心脏自噬的影响  

Changes of polyamine metabolism and autophagy in aging heart and effect of exogenous spermidine on autophagy in aged rat heart

作　　者：吴飞翔 陈俞翰 李邵琦 王举 林岩[2] 王俊莹 张昊 于雪 赵雅君 WU Fei-xiang;CHEN Yu-han;LI Shao-qi;WANG Ju;LIN Yan;WANG Jun-ying;ZHANG Hao;YU Xue;ZHAO Ya-jun(Dept of Pathophysiology,School of Basic Medicine,Harbin Medical University,Harbin 150081,China;Dept of Pathophysiology,School of Basic Medicine,Qiqihar Medical University,Qiqihar Heilongjiang 161006,China)

机构地区：[1]哈尔滨医科大学基础医学院病理生理学教研室,黑龙江哈尔滨150081 [2]齐齐哈尔医学院基础医学院病理生理学教研室,黑龙江齐齐哈尔161006

出　　处：《中国药理学通报》2019年第8期1073-1079,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81170178);国家自然科学基金应急管理项目(No 31751004)

摘　　要：目的 探讨增龄大鼠心脏多胺代谢与自噬的变化规律,以及精脒对衰老心脏自噬的影响。方法 Westen blot法检测3、6、12、24月龄大鼠心肌多胺合成与分解代谢限速酶ODC与SSAT表达,自噬相关蛋白LC3-Ⅱ/Ⅰ与p62的表达;检测3、24月龄及给予精脒6周的24月龄大鼠心肌ATG5、ATG7、p16表达。观察心肌自噬小体形成、计算细胞横截面积及细胞凋亡率、检测活性氧(ROS)产生。结果 随年龄增加,心肌ODC与LC3-Ⅱ/Ⅰ表达降低,SSAT与p62表达增加。24月龄大鼠心肌p16表达增加,细胞横截面积增大,细胞凋亡及ROS产生增多,自噬小体减少,p62表达增加,LC3-Ⅱ/Ⅰ、ATG5和ATG7表达降低。精脒干预后能明显抑制衰老诱导的以上指标的改变。结论 随着年龄增加,大鼠心肌多胺合成代谢下调,分解代谢上调,细胞自噬能力下降。外源性精脒可能通过诱导心肌细胞自噬延缓大鼠心脏老化。Aim To discuss the changes of polyamine metabolism and autophagy in aging rat heart and the effect of exogenous spermidine on autophay in aged rat heart.Methods Western blot assay was used to detect the expressions of ODC and SSAT-rate-limiting enzyme of polyamine anabolism and catabolism as well as the expression of autophagy-relevant protein LC3Ⅱ/Ⅰ and p62 in cardiac tissues from male Wistar rats aged 3,6,12 and 24 months,and the expressions of p16,LC3Ⅱ/Ⅰ,ATG5 and ATG7 protein were detected in cardiac tissues in rats aged 3 months,24 months and 24 months with spermidine administrtion,respectively.The myocardial autophagosome formation was observed by transmission electron microscope.In addition,cell cross-sectional area,cell apoptosis rate and generation of ROS were evaluated.Results With heart aging in rats,ODC expression and LC3Ⅱ/Ⅰ ratio were degraded,and SSAT and p62 protein expression upgraded.In rats aged 24 months,myocardium showed increased p16 expression,cell cross-sectional area,cell apoptosis and ROS generation,while cell autophagosome formation decreased,p62 expression increased,the expression of LC3Ⅱ/Ⅰ,ATG5 and ATG7 all declined.Spermidine intervention obviously inhibited myocardial changes induced by aging,showing decrease in cell cross-sectional area,apoptosis,ROS generation and p62 expression,and increase in LC3Ⅱ/Ⅰ,ATG5 and ATG7 expression.Conclusions With heart aging in rats,polyamine anabolism is degraded,catabolism is upgraded,and cell autophagy declined.Exogenous spermidine might delay aging through inducing autophagy of cardiomyocytes.

关 键 词：衰老 心脏 多胺代谢 自噬 氧化应激 精脒 

分 类 号：R-332[医药卫生] R322.11