膳食铜补充对大鼠心肌梗死后心肌
基质金属蛋白酶 2表达水平及血流动力学
的影响

doi:10.3877/cma.j.issn.2095-655X.2024.03.005

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摘要目的探讨膳食铜补充对大鼠心肌梗死（MI）后心肌基质金属蛋白酶 2(MMP-2)表达水平及血流动力学的影响。方法取成年雄性SD大鼠40只，6~8周龄，体重（260±15）g。采用随机数字表法，分为假手术对照组(对照组，n=10），MI组（n=15）和膳食铜补充组（MI-铜组，n=15）。MI组和MI-铜组进行MI模型制作，对照组进行MI假手术。MI-铜组给予充足铜饮食（20mg/kg），对照组与MI 组给予铜饮食（6mg/kg）。精心饲养4周后，电生理仪中导出大鼠手术前后ST段偏移值，检测大鼠左心室舒张末压（LVDEP）、左心室收缩压(SYS)、平均动脉压（MBP）、左心室内压最大上升速率(+LVdp/dtmax)与左心室内压最大下降速率(-LVdp/dtmax）。Masson染色镜下观察大鼠MI后病理变化，应用酶联免疫吸附试验检测心肌MMP-2表达水平。采用配对t检验比较手术前后ST段偏移值，采用单因素方差分析及LSD-t检验比较组间血流动力学指标及MMP-2表达水平。结果造模后，对照组成活8只，MI组成活8只，MI-铜组成活10只。MI组+MI-铜组心电ST段偏移值术后［（33.00±3.24）mV］与术前［(2.90±1.14)mV］比较，明显升高(t=-44.303，P＜0.01)。MI-铜组LVDEP［（24.10±0.75）mmHg］（1mmHg=0.133kPa）较MI组［（32.49±1.82）mmHg］明显降低（t=-15.93，P＜0.01），MI组与MI-铜组LVDEP均较对照组［（1.41±0.09）mmHg］明显升高（t=55.93，43.03，均P＜0.01）。MI-铜组SYS［（75.18±2.33）mmHg］、MBP［（62.54±1.86）mmHg］、+LVdp/dtmax［（2592.00±192.52）mmHg/s］、-LVdp/dtmax［（2188.00±286.15）mmHg/s］均较MI组［（65.20±1.63）mmHg，（55.90±1.66）mmHg、（1722.50±162.28）mmHg/s，（1643.75±101.55）mmHg/s］明显升高（t=6.12，4.41，10.36，5.76；均P＜0.01），MI组与MI-铜组SYS、MBP、+LVdp/dtmax、-LVdp/dtmax均较对照组［（112.31±5.42）mmHg，（104.19±5.10）mmHg，（5839.75±170.21）mmHg/s，（4693.75±120.70）mmHg/s］明显降低（t=-27.35，30.40，-46.52，-30.65，-22.72，-27.64，-38.68，-26.54；均P＜0.01）。对照组左心室心肌厚度均匀，心室腔正常；MI组和MI-铜组可见左心室梗死区域心肌明显变薄，胶原纤维Masson染色呈蓝色；MI-铜组与MI组比较，心室心肌病理损伤有不同程度的改善。MI-铜组MMP-2表达水平［(116.12±14.33)μg/L］较MI组［(147.27±1.79)μg/L］明显减低(t=-5.37，P＜0.01)，MI组与MI-铜组MMP-2均较对照组［（83.93±9.34）μg/L］明显升高（t=10.53，5.73；均P＜0.01）。结论膳食铜补充可抑制心肌MMP-2表达水平，改善大鼠MI后心脏血流动力学指标，在一定程度上减轻心肌病理损伤。

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关键词 ：心肌梗死, 膳食, 铜, 基质金属蛋白酶 2, 血流动力学

Abstract：ObjectiveTo explore the effect of dietary copper supplementation on the expression of myocardial matrix metalloproteinase 2 (MMP-2) and hemodynamics after myocardial infarction (MI) in rats. MethodsForty adult male Sprague-Dawley rats, aged 6-8 weeks and weighing (260±15)g, were selected. Rats were divided into a sham operation control group (control group, n=10), an MI group (n=15), and a dietary copper supplementation group (MI-Cu group, n=15) using the method of random number table. MI models were made in MI group and MI-Cu group, and control group performed sham MI operation. The MI-Cu group was given an adequate copper diet (20mg/kg), and the control group and the MI group were given a copper diet (6mg/kg). After 4 weeks of careful feeding, the pre-and post-operative ST segment deviation values of rats was exported from the electrophysiological instrument. The left ventricular end diastolic pressure (LVDEP), left ventricular systolic pressure (SYS), mean arterial pressure (MBP), maximal rate of increase of left ventricular pressure (+LVdp/dtmax), and maximal rate of decrease of left ventricular pressure (-LVdp/dtmax) were detected. The pathological changes after MI in rats were observed under a microscope after Masson staining. The expression of myocardial MMP-2 in rats was detected by enzyme linked immunosorbent assay. Paired t-test was used to compare the ST segment deviation values before and after surgery. One-way analysis of variance and LSD-t test were used to compare the hemodynamic indexes and MMP-2 expression levels between groups. ResultsAfter the model was established, 8 rats survived in the control group, 8 rats survived in the MI group, and 10 rats survived in the MI-Cu group. The ST segment deviation value of the electrocardiogram in the MI group and MI-Cu group after surgery ［(33.00±3.24)mV］ was significantly higher than that before surgery ［(2.90±1.14)mV］ (t=-44.303, P＜0.01). LVDEP in the MI-Cu group ［(24.10±0.75)mmHg, 1mmHg=0.133kPa］ was significantly lower than that in the MI group ［(32.49±1.82)mmHg］ (t=-15.93, P＜0.01). LVDEP in the MI group and the MI-Cu group were significantly higher than that in the control group ［(1.41±0.09)mmHg］ (t=55.93, 43.03, all P＜0.001). SYS ［(75.18±2.33)mmHg］, MBP ［(62.54±1.86)mmHg］, +LVdp/dtmax［(2592.00±192.52)mmHg/s］, and -LVdp/dtmax ［(2188.00±286.15)mmHg/s］ in the MI-Cu group were significantly higher than those in the MI group ［(65.20±1.63)mmHg, (55.90±1.66)mmHg, (1722.5±162.28)mmHg/s, (1643.75±101.55)mmHg/s］(t=6.12, 4.41, 10.36, 5.76, all P＜0.01). SYS, MBP, +LVdp/dtmax, and -LVdp/dtmax in the MI group and MI-Cu group were significantly lower than those in the control group ［(112.31±5.42)mmHg, (104.19±5.10)mmHg, (5839.75±170.21)mmHg/s, (4693.75±120.70)mmHg/s］ (t=-27.35, 30.40, -46.52, -30.65, -22.72, -27.64, -38.68, -26.54, all P＜0.01). In the control group, the left ventricular myocardial thickness was uniform and the ventricular cavity was normal. In the MI group and MI-Cu group, the MI area of the left ventricle was significantly thinner, and the collagen fibers were blue. The pathological damage of ventricular myocardium in the MI-Cu group was improved to some extent compared with the MI group. The expression level of MMP-2 in the MI-Cu group［(116.12±14.33)μg/L］ was significantly lower than that in the MI group ［(147.27±1.79) μg/L］ (t=-5.37, P＜0.01). The expression levels of MMP-2 in the MI group and MI-Cu group were significantly higher than that in the control group ［(83.93±9.34)μg/L］ (t=10.53, 5.73, all P＜0.01). ConclusionDietary copper supplementation can inhibit the expression level of myocardial MMP-2, improve the hemodynamic indexes of the heart after MI in rats, and reduce myocardial pathological damage to a certain extent.

Key words： Miocardial infarction Diet Copper Matrix metalloproteinase 2 Hemodynamics

收稿日期: 2024-06-05

基金资助:海南省卫生健康行业科研项目（21A200228）；海南省临床医学中心建设项目（琼卫医函〔2021〕75 号）；大学生创新创业训练计划项目（S202311810044）

通讯作者: 刘聪辉， Email：517384568＠qq.com

引用本文:

刘聪辉何浩然黄一诺张凤王凡月郝翰. 膳食铜补充对大鼠心肌梗死后心肌基质金属蛋白酶 2表达水平及血流动力学的影响[J]. 中华诊断学电子杂志, 2024, 12(3): 166-172.
Liu Conghui1, He Haoran2, Huang Yinuo2, Zhang Feng2, Wang Fanyue2, Hao Han2. Effect of dietary copper supplementation on the expression level of myocardial matrix metalloproteinase 2 and hemodynamics after myocardial infarction in rats. zhzdx, 2024, 12(3): 166-172.

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［1］Cao Y，Lu Z，Wang D，et al.Therapeutic evaluation and metabolic reprograming of isosteviol sodium in a rat model of ischemic cardiomyopathy［J］.Eur J Pharmacol，2021（911）：174539.DOI：10.1016/j.ejphar.2021.174539. ［2］Ghalibaf AM，Soflaei SS，Ferns GA，et al.Association between dietary copper and cardiovascular disease：a narrative review［J］.J Trace Elem Med Biol，2023（80）：127255.DOI：10.1016/j.jtemb.2023.127255. ［3］《中国心血管健康与疾病报告2022》编写组.《中国心血管健康与疾病报告2022》要点解读［J］.中国心血管杂志,2023,28(4):297-312.DOI:10.3969/j.issn.1007-5410.2023.04.001. ［4］刘聪辉，贺兆发，刘春辉，等.姜黄素对急性心肌梗死大鼠心功能及心肌纤维化的作用［J］.心血管康复医学杂志，2015(4):407-410.DOI：10.3969/j.issn.1008-0074.2015.04.17. ［5］Wei SL， Cheng XD， Li J， et al. Venoarterial extracorporeal membrane oxygenation improves survival in a rat model of acute myocardial infarction［J］.Artif Organs，2023，47(7):1163-1173.DOI：10.1111/aor.14499. ［6］Wang XY，Gaur M，Mounzih K，et al.Inhibition of galectin-3 post-infarction impedes progressive fibrosis by regulating inflammatory profibrotic cascades［J］.Cardiovasc Res，2023，119(15):2536-2549.DOI：10.1093/cvr/cvad116. ［7］Mahinrad S，Vriend AE，Jukema JW，et al.Left ventricular hypertrophy and cognitive decline in old age［J］.J Alzheimers Dis，2017，58(1):275-283.DOI：10.3233/JAD-161150. ［8］Elsherif L， Wang L， Saari JT， et al. Regression of dietary copper restriction-induced cardiomyopathy by copper repletion in mice［J］.J Nutr，2004，134(4):855-860.DOI：10.1093/jn/134.4.855. ［9］Kitala K，Tanski D，Godlewski J，et al.Copper and zinc particles as regulators of cardiovascular system function-a review［J］.Nutrients，2023，15(13):3040.DOI：10.3390/nu15133040. ［10］Hughes BG,Schulz R.Targeting MMP-2 to treat ischemic heart injury［J］.Basic Res Cardiol,2014,109(4):424.DOI:10.1007/s00395-014-0424-y. ［11］Frantz S，Hundertmark MJ，Schulz-Menger J，et al.Left ventricular remodelling post-myocardial infarction：pathophysiology，imaging，and novel therapies［J］.Eur Heart J，2022，43(27):2549-2561.DOI：10.1093/eurheartj/ehac223. ［12］Liu MR，López de Juan Abad B，Cheng K.Cardiac fibrosis：myofibroblast-mediated pathological regulation and drug delivery strategies［J］.Adv Drug Deliv Rev，2021（173）：504-519.DOI：10.1016/j.addr.2021.03.021. ［13］Trumbo P，Yates AA，Schlicker S，et al.Dietary reference intakes：vitamin A，vitamin K，arsenic，boron，chromium，copper，iodine，iron，manganese，molybdenum，nickel，silicon，vanadium，and zinc［J］.J Am Diet Assoc，2001,101(3):294-301.DOI:10.1016/s0002-8223(01)00078-5. ［14］Bassiouni W，Ali M，Schulz R.Multifunctional intracellular matrix metalloproteinases：implications in disease［J］.FEBS J，2021，288(24):7162-7182.DOI：10.1111/febs.15701. ［15］Sariahmetoglu M，Skrzypiec-Spring M，Youssef N，et al.Phosphorylation status of matrix metalloproteinase 2 in myocardial ischaemia-reperfusion injury［J］.Heart，2012，98(8):656-662.DOI：10.1136/heartjnl-2011-301250. ［16］Skrzypiec-Spring M， Urbaniak J， Sapa-Wojciechowska A， et al.Matrix metalloproteinase-2 inhibition in acute ischemia-reperfusion heart injury-cardioprotective properties of carvedilol［J］.Pharmaceuticals (Basel)，2021，14(12):1276.DOI：10.3390/ph14121276. ［17］Hayashidani S，Tsutsui H，Ikeuchi M，et al.Targeted deletion of MMP-2 attenuates early LV rupture and late remodeling after experimental myocardial infarction［J］.Am J Physiol Heart Circ Physiol，2003，285(3):H1229-1235.DOI：10.1152/ajpheart.00207.2003. ［18］Goodman JR，Warshaw JB，Dallman PR.Cardiac hypertrophy in rats with iron and copper deficiency：quantitative contribution of mitochondrial enlargement［J］.Pediatr Res，1970，4(3):244-256.DOI：10.1203/00006450-197005000-00003. ［19］Liu Y，Miao J.An emerging role of defective copper metabolism in heart disease［J］.Nutrients，2022，14(3)：700.DOI：10.3390/nu14030700. ［20］Jiang Y，Reynolds C，Xiao C，et al.Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice［J］.J Exp Med，2007，204(3):657-666.DOI：10.1084/jem.20061943. ［21］Hughes WM Jr， Rodriguez WE， Rosenberger D， et al. Role of copper and homocysteine in pressure overload heart failure［J］.Cardiovasc Toxicol，2008，8(3):137-144.DOI：10.1007/s12012-008-9021-3. ［22］Nguyen YT，Kim N，Lee HJ.Metal complexes as promising matrix metalloproteinases regulators［J］.Int J Mol Sci，2023，24(2):1258.DOI：10.3390/ijms24021258. ［23］Horowitz JD，Chong CR.Matrix metalloproteinase-2 activation：critical to myocardial contractile dysfunction following ischaemia-reperfusion［J］.Cardiovasc Res，2020，116(5):876-878.DOI：10.1093/cvr/cvz271.