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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

26卷

期数:

2020年03期

页码:

213-217

栏目:

基础医学

出版日期:

2020-06-10

文章信息/Info

Title:

Study of methionine-induced ventricular remodeling

文章编号:

1006-8147(2020)03-0213-05

作者:

涂代苗; 阚晨星; 马向红

（天津医科大学第二医院心脏科，天津市心血管病离子与分子机能重点实验室, 天津心脏病学研究所，天津300211）

Author(s):

TU Dai-miao;  KAN Chen-xing;  MA Xiang-hong

（Department of Cardiology, The Second Hospital, Tianjin Medical University, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Tianjin 300211, China)

关键词:

蛋氨酸; 同型半胱氨酸; 高同型半胱氨酸血症; 心室重塑; PDCD4通路

Keywords:

methionine; homocysteine; high homocysteinemia; ventricular remodeling; PDCD4 signal pathway

分类号:

R541.6+1

DOI:

-

文献标志码:

A

摘要:

目的：探讨口服蛋氨酸饲料致大鼠心力衰竭模型的机制，及程序性死亡因子4（PDCD4）通路在此过程中的作用。方法：5周龄健康Wistar雄性大鼠30只，适应性喂养1周后，随机分为实验组与对照组，实验组给予3%蛋氨酸饲料喂养，对照组标准饲料喂养。12周后进行血流动力学检测，采用酶联免疫法测定血清同型半胱氨酸（HCY）及N端前脑钠肽（NT-proBNP）水平，心脏彩超进行心功能评估，病理染色明确有无细胞肥大、纤维化，Western blot检测心肌组织中PDCD4蛋白的表达。结果：3%蛋氨酸饲料喂养组HCY水平较对照组升高（均P＜0.05）,心脏彩超提示3%蛋氨酸饲料喂养组大鼠左室射血分数、缩短分数、室间隔厚度显著减低（均P＜0.05），左室收缩末内径及舒张末内径较对照组显著增加（均P＜0.05），Western blot结果显示, PDCD4蛋白表达降低（P＜0.05）。结论：通过口服蛋氨酸饲料造成大鼠高HCY血症可导致大鼠出现心室重塑，并造成心功能受损，其机制可能与PDCD4信号通路的下调有关。

Abstract:

Objective: To investigate the mechanism of methionine-induced heart dysfunction in rats and the role of programmed cell death factor (PDCD4) pathway in this process. Methods: Thirty healthy male Wistar rats were randomly divided into control group or 3% methionine forage fed group after adaptive feeding for 1 week. Twelve weeks later, the hemodynamic assessment were performed. The level of serum homocysteine (HCY) and N-terminal B-type natriuretic peptide (NT-proBNP) were determined by enzyme-linked immunosorbent assays. The cardiac function was evaluated by color Doppler echocardiography, and the ventricular changes were confirmed by pathological stains. Finally, the expression of PDCD4 in ventricle was detected by Western blot. Results: The level of HCY in the experimental group was higher than that in the control group(P＜0.05). Echocardiographic showed the left ventricular ejection fraction, fractional shortening, interventricular septal thickness in the experimental rats were decreasing(all P＜0.05), while the left ventricular end diastolic dimension and left ventricular end systolic dimension were increasing compared to the control rats (all P＜0.05). Besides, the expression of protein PDCD4 was lower in experimental rats(P＜0.05). Conclusion: High homocysteinemia induced by methionine feed can lead to myocardial dysfunction and ventricular remodeling in rats, and it may be related to the down-regulation of PDCD4 signaling pathway.

参考文献/References:

[1] Abdel-Aty H, Zagrosek A, Schulz-Menger J, et al. Delayed enhancement and T2-weighted cardiovascular magnetic resonance imaging differentiate acute from chronic myocardial infarction[J]. Circulation, 2004, 109(20):2411
[2] 中华医学会心血管病学分会心力衰竭学组,中国医师协会心力衰竭专业委员会,中华心血管病杂志编辑委员会, 等. 中国心力衰竭诊断和治疗指南2018[J]. 中华心力衰竭和心肌病杂志:中英文,2018, 2(4):196
[3] Kumar A, Palfrey H A, Pathak R, et al. The metabolism and significance of homocysteine in nutrition and health[J]. NutrMetab (Lond),2017, 14:78
[4] 徐西子, 董昭杰, 马向红.血同型半胱氨酸水平与冠心病慢性心衰严重程度的相关性分析[J]. 天津医科大学学报, 2017, 23(3):221
[5] 马向红,黄体钢,周丽娟,等. 同型半胱氨酸对大鼠主动脉内皮细胞分泌一氧化氮、血管紧张素Ⅱ、内皮素的影响[J]. 中国心血管杂志, 1998, 3(5):344
[6] Kunkel G H, Chaturvedi P, Tyagi S C. Resuscitation of a dead cardiomyocyte[J]. Heart Fail Rev, 2015, 20(6):709
[7] 中华医学会心血管病学分会,中华心血管病杂志编辑委员会. 慢性心力衰竭诊断治疗指南[J].中华心血管病杂志, 2007, 35(12):1076
[8] Khadka D, Kim H J, Oh G S, et al. Augmentation of NAD(+) levels by enzymatic action of NAD(P)H quinone oxidoreductase 1 attenuates adriamycin-induced cardiac dysfunction in mice[J]. J Mol Cell Cardiol, 2018, 124(124):45
[9] Houser S R, Margulies K B, Murphy A M, et al. Animal models of heart failure a scientific statement from the American Heart Association[J]. Circ Res, 2012, 111(1):131
[10] Valero-Munoz M, Backman W, Sam F. Murine models of heart failure with preserved ejection fraction:a fishing expedition[J]. JACC Basic Transl Sci , 2017,2(6):770
[11] Xiao Y, Su X, Huang W, et al. Role of S-adenosylhomocysteine in cardiovascular disease and its potential epigenetic mechanism[J]. Int J Biochem Cell Biol, 2015, 67:158
[12] Wang C, Han L, Wu Q, et al. Association between homocysteine and incidence of ischemic stroke in subjects with essential hypertension: a matched case-control study[J]. Clin Exp Hypertens, 2015, 37(7):557
[13] Yang B, Fan S, Zhi X, et al. Prevalence of hyperhomocysteinemia in China: a systematic review and meta-analysis[J].Nutrients, 2015,7(1):74
[14] 张国领,张林,刘桂萍. 高同型半胱氨酸血症的临床研究进展[J].中国医药导报, 2018,15(20):29
[15] Wang J, Ouyang N, Qu L, et al. Effect of MTHFR A1298C and MTRR A66G genetic mutations on homocysteine levels in the Chinese population: a systematic review and meta-analysis[J]. J Transl Int Med, 2017, 5(4):220
[16] Liu B, Ma S T, Wang T, et al. A novel rat model of heart failure induced by high methionine diet showing evidence of association between hyperhomocysteinemia and activation of NF-kappaB[J]. Am J Transl Res, 2016, 8(1):117
[17] 王成艳,赵东岳,胡兴亚. 口服蛋氨酸造成的大鼠肾间质纤维化模型及其机制研究[J]. 海峡科学, 2015(11):28
[18] 任晓丽,杨波,黄陈平,等. 高蛋氨酸饮食对大鼠血管内皮细胞分泌功能的影响[J]. 氨基酸和生物资源, 2010, 32(4):50
[19] 孟斌,高蔚娜,杨继军,等. 高蛋氨酸饲料喂养的大鼠高同型半胱氨酸血症模型的实验研究[J]. 氨基酸和生物资源, 2011, 33(2):53
[20] Korai M, Kitazato K T, Tada Y, et al. Hyperhomocysteinemia induced by excessive methionine intake promotes rupture of cerebral aneurysms in ovariectomized rats[J]. J Neuroinflammation, 2016, 13(1):165

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备注/Memo

备注/Memo:

基金项目 天津医科大学第二医院青年基金项目资助（2017ydey18）
作者简介 涂代苗（1993-），女，硕士在读，研究方向：心血管内科；通信作者：马向红，E-mail: ma_xianghong@163.com。

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更新日期/Last Update: 2020-06-13