[1]吴飞翔,陈俞翰,李邵琦,等.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[J].中国药理学通报,2019,(08):1073-1079.[doi:10.3969/j.issn.1001-1978.2019.08.009]
 WU Fei-xiang,CHEN Yu-han,LI Shao-qi,et al.Changes of polyamine metabolism and autophagy in aging heart and effect of exogenous spermidine on autophagy in aged rat heart[J].Chinese Pharmacological Bulletin,2019,(08):1073-1079.[doi:10.3969/j.issn.1001-1978.2019.08.009]
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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()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2019年08期
页码:
1073-1079
栏目:
论著
出版日期:
2019-08-14

文章信息/Info

Title:
Changes of polyamine metabolism and autophagy in aging heart and effect of exogenous spermidine on autophagy in aged rat heart
文章编号:
1001-1978(2019)08-1073-07
作者:
吴飞翔1陈俞翰1李邵琦1王 举1林 岩2王俊莹1张 昊1于 雪1赵雅君1
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
Author(s):
WU Fei-xiang1 CHEN Yu-han1 LI Shao-qi1 WANG Ju1 LIN Yan2 WANG Jun-ying1 ZHANG Hao1 YU Xue1 ZHAO Ya-jun1
1.Dept of Pathophysiology, School of Basic Medicine, Harbin Medical University, Harbin 150081, China; 2.Dept of Pathophysiology, School of Basic Medicine, Qiqihar Medical University, Qiqihar Heilongjiang 161006, China
关键词:
衰老 心脏 多胺代谢 自噬 氧化应激 精脒
Keywords:
aging heart polyamine metabolism autophagy oxidative stress spermidine
分类号:
R-332; R322.11; R329.24; R339.38; R349.1; R916.4
DOI:
10.3969/j.issn.1001-1978.2019.08.009
文献标志码:
A
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。
Abstract:
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.

参考文献/References:

[1] Ren J, Zhang Y.Targeting autophagy in aging and aging-related cardiovascular diseases[J].Trends Pharmacol Sci, 2018, 39(12): 1064-76.
[2] 王 敏,余 薇,查文良.自噬和线粒体自噬在糖尿病心肌病中的作用研究进展[J].中国药理学通报,2018,34(10):1337-40.
[2] Wang M, Yu W, Zha W L.Research progress of autophagy and mitochondrial autophagy in diabetic cardiomyopathy[J].Chin Pharmacol Bull,2018, 34(10):1337-40.
[3] 刘小莺,吴 莉,陈 洲,等.PTEN抑制剂对高糖诱导的内皮细胞衰老的影响[J].中国药理学通报,2016,32(4):514-9.
[3] Liu X Y, Wu L, Chen Z, et al.PTEN inhibitors attenuates high glucose induced endothelial cell senescence[J].Chin Pharmacol Bull,2016,32(4): 514-9.
[4] Zhang Y, Wang C, Zhou J, et al.Complex inhibition of autophagy by mitochondrial aldehyde dehydrogenase shortens lifespan and exacerbates cardiac aging [J].Biochim Biophys Acta Mol Basis Dis,2017, 1863(8): 1919-32.
[5] Madeo F, Bauer M A, Carmona-Gutierrez D, et al.Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans[J]? Autophagy,2019, 15(1): 165-8.
[6] Wang W, Zhang H, Xue G, et al.Exercise training preserves ischemic preconditioning in aged rat hearts by restoring the myocardial polyamine pool [J].Oxid Med Cell Longev,2014,2014: 457429.
[7] Nishimura K.Decrease in polyamines with aging and their ingestion from food and drink [J].J Biochem,2006, 139(1): 81-90.
[8] Minois N, Carmona-Gutierrez D, Madeo F.Polyamines in aging and disease [J].Aging(Albany NY),2011, 3(8): 716-32.
[9] 李 昂,邢雅琪,李晓霞,等.氧化应激中ROS对 FOXO3a 转录因子的调控作用研究进展[J].中国药理学通报,2016,32(9):1203-7.
[9] Li A, Xing Y Q, Li X X, et al.Redox regulation of FOXO3a transcription factor[J].Chin Pharmacol Bull,2016, 32(9): 1203-7.
[10] Rottenberg H, Hoek J B.The path from mitochondrial ROS to aging runs through the mitochondrial permeability transition pore[J].Aging Cell,2017, 16(5): 943-55.
[11] Rider J E, Hacker A, Mackintosh C A, et al.Spermine and spermidine mediate protection against oxidative damage caused by hydrogen peroxide [J].Amino Acids,2007, 33(2): 231-40.
[12] 薛 过, 王伟伟, 赵雅君, 等.外源性多胺对老年大鼠抗衰老作用的实验研究[J].中国药理学通报,2011,27(8):1135-8.
[12] Xue G, Wang W W, Zhao Y J, et al.Experimental study on anti-aging effects of exogenous polyamines on aged rats [J].Chin Pharmacol Bull,2011, 27(8): 1135-8.
[13] Eisenberg T, Abdellatif M, Schroeder S, et al.Cardioprotection and lifespan extension by the natural polyamine spermidine [J].Nat Med,2016, 22(12): 1428-38.
[14] Zhang H, Wang J, Li L, et al.Spermine and spermidine reversed age-related cardiac deterioration in rats[J].Oncotarget,2017, 8(39): 64793-808.

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备注/Memo

备注/Memo:
收稿日期:2019-04-12,修回日期:2019-05-18
基金项目: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)
作者简介:吴飞翔(1991-),女,硕士生,研究方向:心脏老化的机制,E-mail:xjysecurewfx@163.com;
赵雅君(1964-),女,博士,研究员,博士生导师,研究方向:心脏老化的机制,通讯作者:Tel:0451-86674548, E-mail:zhaoyajun1964@163.com
更新日期/Last Update: 2019-08-14