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[1]黄 伟.有氧运动对衰老大鼠心肌保护作用的机制研究[J].山东体育科技,2013,06:0.
 HUANG Wei.Mechanism of aerobic exercise training on myocardium of old rats[J].,2013,06:0.
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有氧运动对衰老大鼠心肌保护作用的机制研究

《山东体育科技》[ISSN:1009-9840/CN:37-1011/G8]

期数:
2013年06期
页码:
0
栏目:
出版日期:
2013-12-25

文章信息/Info

Title:
Mechanism of aerobic exercise training on myocardium of old rats
作者:
黄 伟
郑州大学 体育学院, 河南 郑州 450044
Author(s):
HUANG Wei
Physical Education College,Zhengzhou University,Zhengzhou 450044,Henan,China
关键词:
跑台运动衰老大鼠基质金属蛋白酶细胞外基质心脏
Keywords:
treadmill running old rats matrix metalloproteinase extracellular matrix heart
分类号:
G804.7
DOI:
-
文献标识码:
A
摘要:
目的:观察10周有氧运动对衰老大鼠心肌胶原沉积的影响并探讨转化生长因子-β/基质金属蛋白酶组织抑制剂-1/基质金属蛋白酶(TGF-β/TIMP-1/MMPs)信号通路是否参与了运动对衰老大鼠心肌的保护作用。方法:30只雄性SD大鼠随机分为青年对照组(YC组),衰老对照组(OC组)和衰老运动组(OE组),每组10只。OE组进行10周跑台运动,YC组和OC组保持安静状态。实验后用左心室导管法测定血液动力学参数,包括左心室收缩期压力(LVSP)、左心室舒张末期压力(LVEDP)、左心室压力最大上升速率(+dp/dtmax)和左室压力最大下降速率(-dp/dtmax)。动物处死后用Masson染色检测心肌胶原容积分数(CVF),实时荧光定量PCR 检测I、III型胶原纤维mRNA表达,Western blot检测MMP前体(Pro-MMPs)、活性MMPs(MMPs)、TGF-β和TIMP-1蛋白表达水平。结果:与YC组比较,OC组LVSP、±dp/dtmax下降(均为P<0.01),LVEDP升高(P<0.01);CVF升高(P<0.01);I、III型胶原mRNA升高(均为P<0.01);Pro-MMP-2、MMP-1、MMP-2、MMP-3和MMP-14蛋白降低(均为P<0.01),Pro-MMP-3、TGF-β和TIMP-1蛋白升高(均为P<0.01)。与OC组比较,OE组LVSP、±dp/dtmax升高(均为P<0.01),LVEDP下降(P<0.01);CVF下降(P<0.01);I、III型胶原mRNA降低(分别为P<0.01和P<0.05);Pro-MMP-2和Pro-MMP-3蛋白升高(均为P<0.01),Pro-MMP-14、MMP-1、MMP-2、MMP-3、MMP-14、TGF-β和TIMP-1蛋白降低(均为P<0.01)。结论:10周跑台运动通过抑制胶原合成并促进其降解延缓了心脏衰老过程中的胶原沉积和心肌纤维化并改善心功能,其机制与TGF-β/TIMP-1信号通路受到抑制,MMPs表达上调有关。
Abstract:
Objective:To observe the effects of 10-week treadmill running on myocardium collagen deposition and to explore whether transforming growth factor-β/tissue inhibitors of metalloproteinase-1/matrix metalloproteinase (TGF-β/TIMP-1/MMPs) signal pathway is involved in the protective effect of exercise on myocardium of old rats.Methods:30 male SD rats were randomly divided into young control group (YC), old control group (OC) and old exercise group (OE) and each group had 10 animals. Rats in OE group performed 10-week treadmill running while YC and OC group maintained resting state. After experiment, hemodynamic parameters were measured with pressure transducer inserted retrograde in left ventricle including left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximal developing rate of left ventricular pressure (+dp/dtmax) and maximal descending rate of left ventricular pressure (-dp/dtmax). Heart tissue was collected for collagen volume fraction (CVF) by Masson staining after sacrifice of animal. Collagen fiber I and III mRNA were determined by real-time fluorescent quantitation PCR, while protein level of Pro-MMPs, active MMPs (MMPs), TGF-β and TIMP-1 by Western blot. Results: Compared with YC group, LVSP and ±dp/dtmax reduced (both P<0.01), LVEDP raised (P<0.01); CVF elevated (P<0.01); mRNA of collagen fiber I and III increased (both P<0.01); Pro-MMP-2, MMP-1, MMP-2, MMP-3 and MMP-14 protein decreased (all P<0.01), Pro-MMP-3, TGF-β and TIMP-1 protein heightened (all P<0.01) in OC group. Compared with OC group, LVSP and ±dp/dtmax raised (both P<0.01), LVEDP reduced (P<0.01); CVF lowered (P<0.01); mRNA of collagen fiber I and III decreased (P<0.01 and P<0.05 respectively); Pro-MMP-2 and Pro-MMP-3 protein heightened (both P<0.01), Pro-MMP-14, MMP-1, MMP-2, MMP-3, MMP-14, TGF-β and TIMP-1 protein decreased (all P<0.01). Conclusion: Treadmill running of 10 weeks delayed myocardium collagen deposition and fibrosis and improved cardiac function by inhibition of collagen synthesis and promotion of its degradation in old rats, the mechanism of which was related with the inhibition of TGF-β/TIMP-1 signal pathway and upregulation of MMPs.

参考文献/References

[1]Zhang P, Su J, Mende U. Cross talk between cardiac myocytes and fibroblasts: from multiscale investigative approaches to mechanisms and functional consequences[J]. Am J Physiol Heart Circ Physiol, 2012,303(12):1385-1396. [2]Horn MA, Graham HK, Richards MA,et al.Age-related divergent remodeling of the cardiac extracellular matrix in heart failure: collagen accumulation in the young and loss in the aged[J]. J Mol Cell Cardiol, 2012,53(1):82-90. [3]陈敏, 吴卉卉, 沈晓丽, 等. 基质金属蛋白酶及其抑制因子与扩张型心肌病的关系[J]. 中国组织化学与细胞化学杂志, 2011,20(1):27-32. [4]王永, 赵红佳, 曾凯, 等. 健心颗粒对慢性心衰患者血清MMP-9及TIMP-1的影响[J]. 福建中医药大学学报, 2012,22(4):5-7. [5]赵志杰, 刘新民, 周国鹏, 等. 老龄大鼠肺内基质金属蛋白酶2、9及基质金属蛋白酶组织抑制因子1、2、3表达变化[J]. 北京大学学报(医学版), 2008,40(1):101-104. [6]Kapur NK. Transforming growth factor-beta: governing the transition from inflammation to fibrosis in heart failure with preserved left ventricular function[J]. Circ Heart Fail, 2011,4(1):5-7. [7]Kitzman DW, Herrington DM, Brubaker PH,et al.Carotid arterial stiffness and its relationship to exercise intolerance in older patients with heart failure and preserved ejection fraction[J]. Hypertension, 2013,61(1):112-119. [8]Choi SY, Chang HJ, Choi SI,et al.Long-term exercise training attenuates age-related diastolic dysfunction: association of myocardial collagen cross-linking[J]. J Korean Med Sci, 2009,24(1):32-39. [9]侯伊玲, 薄海, 刘子泉, 等. 运动训练对心肌梗死后心室重构及MMP-2,MMP-9表达的影响[J]. 中国康复医学杂志, 2010,25(3):200-204. [10]Sangaralingham SJ, Huntley BK, Martin FL,et al.The aging heart, myocardial fibrosis, and its relationship to circulating C-type natriuretic Peptide[J]. Hypertension, 2011,57(2):201-207. [11]米粟, 胡卓伟. 抑制心肌纤维化促进心肌再生治疗慢性心血管疾病[J]. 生理科学进展, 2010,41(5):352-358. [12]邓玮, 陈庆伟, 李兴升, 等. 骨髓间充质干细胞经核转录因子κB途径干预心肌纤维化[J]. 中国组织工程研究与临床康复, 2011,15(19):3494-3498. [13]Yengo CM, Zimmerman SD, McCormick RJ,et al.Exercise training post-MI favorably modifies heart extracellular matrix in the rat[J]. Med Sci Sports Exerc, 2012,44(6):1005-1012. [14]Woodiwiss AJ, Oosthuyse T, Norton GR. Reduced cardiac stiffness following exercise is associated with preserved myocardial collagen characteristics in the rat[J]. Eur J Appl Physiol Occup Physiol, 1998,78(2):148-154. [15]Tanaka H, Seals DR. Endurance exercise performance in Masters athletes: age-associated changes and underlying physiological mechanisms[J]. J Physiol, 2008,586(1):55-63. [16]Essa EM, Zile MR, Stroud RE,et al.Changes in plasma profiles of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in stress-induced cardiomyopathy[J]. J Card Fail, 2012,18(6):487-492. [17]Oyamada S, Bianchi C, Takai S,et al.Chymase inhibition reduces infarction and matrix metalloproteinase-9 activation and attenuates inflammation and fibrosis after acute myocardial ischemia/reperfusion[J]. J Pharmacol Exp Ther, 2011,339(1):143-151. [18]Mukherjee R, Snipes JM, Saunders SM,et al.Discordant activation of gene promoters for matrix metalloproteinases and tissue inhibitors of the metalloproteinases following myocardial infarction[J]. J Surg Res, 2012,172(1):59-67. [19]Hao X, Zhang Y, Zhang X,et al.TGF-beta1-mediated fibrosis and ion channel remodeling are key mechanisms in producing the sinus node dysfunction associated with SCN5A deficiency and aging[J]. Circ Arrhythm Electrophysiol, 2011,4(3):397-406. [20]Brooks WW, Conrad CH. Myocardial fibrosis in transforming growth factor beta(1)heterozygous mice[J]. J Mol Cell Cardiol, 2000,32(2):187-195. [21]Chen R, Xue J, Xie ML. Reduction of isoprenaline-induced myocardial TGF-beta1 expression and fibrosis in osthole-treated mice[J]. Toxicol Appl Pharmacol, 2011,256(2):168-173.

备注/Memo

备注/Memo:
郑州大学体育学院院级科研项目资助:运动对心脏衰老的保护作用研究(ZDTY2009-05)
更新日期/Last Update: 1900-01-01