Effect of dapagliflozin on myocardial function changes in early spontaneously hypertensive rats: a study based on longitudinal layer-specific strain

CHEN Xuemei; ZHANG Jun; LI Xin; YAO Ran; LIU Deng; FENG Jiang; TAN Lin; GUO Yanli

doi:10.16016/j.2097-0927.202412094

您当前的位置：

首页 >

文章列表页 >

Effect of dapagliflozin on myocardial function changes in early spontaneously hypertensive rats: a study based on longitudinal layer-specific strain

Basic Medicine | 更新时间：2025-03-28

- Effect of dapagliflozin on myocardial function changes in early spontaneously hypertensive rats: a study based on longitudinal layer-specific strain
- Journal of Army Medical University Vol. 47, Issue 6, Pages: 531-538(2025)
- 作者机构：
  
  陆军军医大学（第三军医大学）第一附属医院超声科，重庆
- 作者简介：
  
  GUO Yanli， E-mail： guoyanli@tmmu.edu.cn
- 基金信息：
  
  the Innovative Leading Talents of Chongqing Talent Program(425Z2K1);the Special Key Project of Technological Innovation and Application Development of Chongqing(CSTB2022TIAD-KPX0153)
- DOI：10.16016/j.2097-0927.202412094
  CLC： R445.1;R554.105;R997.15
- Received：19 December 2024，
  
  Revised：27 December 2024，
  
  Published：30 March 2025
- 稿件说明：
移动端阅览
陈雪梅，张君，李欣，等.基于二维斑点追踪技术的纵向分层应变评价达格列净干预早期自发性高血压大鼠心肌功能变化［J］.陆军军医大学学报，2025，47（06）：531-538.DOI：10.16016/j.2097-0927.202412094.

CHEN X M，ZHANG J，LI X，et al.Effect of dapagliflozin on myocardial function changes in early spontaneously hypertensive rats： a study based on longitudinal layer-specific strain［J］.J Army Med Univ，2025，47（06）：531-538.DOI：10.16016/j.2097-0927.202412094.
陈雪梅，张君，李欣，等.基于二维斑点追踪技术的纵向分层应变评价达格列净干预早期自发性高血压大鼠心肌功能变化［J］.陆军军医大学学报，2025，47（06）：531-538.DOI：10.16016/j.2097-0927.202412094. DOI：

CHEN X M，ZHANG J，LI X，et al.Effect of dapagliflozin on myocardial function changes in early spontaneously hypertensive rats： a study based on longitudinal layer-specific strain［J］.J Army Med Univ，2025，47（06）：531-538.DOI：10.16016/j.2097-0927.202412094. DOI：

摘要

目的

基于二维斑点追踪技术的纵向分层应变参数评估达格列净对早期自发性高血压大鼠（spontaneously hypertensive rat， SHR）心肌功能的作用。

方法

将45只6周龄大小的雄性SHR随机分为3组（

=15）：对照组、达格列净组以及氯沙坦组，达格列净组、氯沙坦组分别以达格列净1 mg/kg、氯沙坦10 mg/kg每天给药喂养连续8周，对照组以等量的生理盐水喂养；同周龄的正常血压雄性Wistar京都大鼠（wistar-kyoto rat，WKY）15只作为空白对照组（WKY组）。每2周对各组行尾动脉收缩压测量、常规超声心动图和二维斑点追踪图像采集及分析，获取左心室心肌各层纵向应变，比较各组参数差异，观察大鼠心肌病理改变。

结果

与WKY组相比，

第8周时，对照组左室收缩功能参数左室射血分数（left ventricular ejection fraction，LVEF）、左室短轴缩短率（left ventricular fraction shortening，LVFS）均下降（

0.05），而达格列净组及氯沙坦组LVEF、LVFS无明显下降。与WKY组相比，在第6周时对照组的心内膜下心肌整体纵向应变（global longitudinal strain of endo-myocardium，GLSendo）已出现下降（

0.05）；第8周时，对照组的GLSendo、中层心肌整体纵向应变（global longitudinal strain of mid-myocardium，GLSmid）及心外膜下心肌整体纵向应变（global longitudinal strain of epi-myocardium，GLSepi）均下降（

0.05）；而达格列净组、氯沙坦组的纵向分层应变参数较WKY组均无统计学差异（

0.05）。病理结果进一步证实，实验第6周时，对照组已出现心肌间质纤维化。

结论

达格列净可有效改善早期SHR的心肌功能。

Abstract

Objective‍　‍To evaluate the effect of dapagliflozin on myocardial function in early spontaneously hypertensive rats (SHR) with layer-specific global longitudinal strain (GLS). Methods‍　‍A total of 45 male SHR aged 6 weeks were randomly divided into control group (normal saline)

dapagliflozin group [1 mg/(kg·day)

]

and losartan group [10 mg/(kg·day)

]

. Fifteen male Wistar-Kyoto (WKY) rats at same age with normal blood pressure were subjected and served as blank control group. During 8 weeks of intervention

systolic blood pressure (SBP) was measured

and conventional echocardiography and two-dimensional speckle tracking echocardiography (2DSTE) were performed and the results were collected to acquire the longitudinal strain of each layer of left ventricular (LV) myocardium. The parameters were compared among the groups. The pathological changes of myocardium were observed in each group of rats. Results‍　‍Compared with the WKY group

LV ejection fraction (LVEF) and LV fraction shortening (LVFS) at week 8 were decreased in the control group (

0.05)

but no such decreases were observed in the dapagliflozin group and the losartan group. The GLS of endo-myocardium (GLSendo) at the 6th week was decreased

and GLSendo

GLSmid and GLSepi at the 8th week were all decreased in the control group than the WKY group (all

0.05). But there were no statistical differences in the above 3 indicators in the dapagliflozin and losartan groups when compared with the WKY group (all

0.05). The pathological results showed that myocardial interstitial fibrosis was observed in the control group at the 6th week

Conclusion‍　‍Dapagliflozin can effectively improve myocardial function in early SHR.

关键词

Keywords

references

GBD 2019 Risk Factors Collaborators . Global burden of 87 risk factors in 204 countries and territories， 1990-2019： a systematic analysis for the Global Burden of Disease Study 2019 ［J］. Lancet ， 2020 ， 396 （ 10258 ）： 1223 - 1249 . DOI： 10.1016/s0140-6736（20）30752-2 http://dx.doi.org/10.1016/s0140-6736（20）30752-2 .

MCEVOY J W ， MCCARTHY C P ， BRUNO R M ， et al . 2024 ESC Guidelines for the management of elevated blood pressure and hypertension ［J］. Eur Heart J ， 2024 ， 45 （ 38 ）： 3912 - 4018 . DOI： 10.1093/eurheartj/ehae178 http://dx.doi.org/10.1093/eurheartj/ehae178 .

WHELTON P K ， CAREY R M ， ARONOW W S ， et al . 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/ APhA /ASH/ASPC/NMA/PCNA guideline for the prevention， detection， evaluation， and management of high blood pressure in adults： a report of the American college of cardiology/American heart association task force on clinical practice guidelines ［J］. Circulation ， 2018 ， 138 （ 17 ）： e484 - e594 . DOI： 10.1161/CIR.0000000000000596 http://dx.doi.org/10.1161/CIR.0000000000000596 .

中国高血压防治指南修订委员会，高血压联盟，中国医疗保健国际交流促进会高血压分会，等 . 中国高血压防治指南（2024年修订版）［J］. 中华高血压杂志， 2024 ， 32 （ 7 ）： 603 - 700 . DOI： 10.16439/j.issn.1673-7245.2024.07.002 http://dx.doi.org/10.16439/j.issn.1673-7245.2024.07.002 .

Revision Committee for Guidelines for prevention and treatment of hypertension in China ， Hypertension Aliance ， Hypertension Branch of China International Exchange and Promotion Association for Medical and Health Care ， et al . （revised in 2024）［J］. Chin J Hypertens ， 2024 ， 32 （ 7 ）： 603 - 700 . DOI： 10.16439/j.issn.1673-7245.2024.07.002 http://dx.doi.org/10.16439/j.issn.1673-7245.2024.07.002 .

NWABUO C C ， VASAN R S . Pathophysiology of hypertensive heart disease： beyond left ventricular hypertrophy ［J］. Curr Hypertens Rep ， 2020 ， 22 （ 2 ）： 11 . DOI： 10.1007/s11906-020-1017-9 http://dx.doi.org/10.1007/s11906-020-1017-9 .

KONG P ， CHRISTIA P ， FRANGOGIANNIS N G . The pathogenesis of cardiac fibrosis ［J］. Cell Mol Life Sci ， 2014 ， 71 （ 4 ）： 549 - 574 . DOI： 10.1007/s00018-013-1349-6 http://dx.doi.org/10.1007/s00018-013-1349-6 .

GARG P ， ASSADI H ， JONES R ， et al . Left ventricular fibrosis and hypertrophy are associated with mortality in heart failure with preserved ejection fraction ［J］. Sci Rep ， 2021 ， 11 （ 1 ）： 617 . DOI： 10.1038/s41598-020-79729-6 http://dx.doi.org/10.1038/s41598-020-79729-6 .

KIM D ， SHIM C Y ， HONG G R ， et al . Differences in left ventricular functional adaptation to arterial stiffness and neurohormonal activation in patients with hypertension： a study with two-dimensional layer-specific speckle tracking echocardiography ［J］. Clin Hypertens ， 2017 ， 23 ： 21 . DOI： 10.1186/s40885-017-0078-9 http://dx.doi.org/10.1186/s40885-017-0078-9 .

ISHIZU T ， SEO Y ， KAMEDA Y ， et al . Left ventricular strain and transmural distribution of structural remodeling in hypertensive heart disease ［J］. Hypertension ， 2014 ， 63 （ 3 ）： 500 - 506 . DOI： 10.1161/HYPERTENSIONAHA.113.02149 http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.02149 .

张君，李欣，刘娟，等 . 分层应变技术评价多柔比星干预大鼠左心室心肌功能［J］. 中国医学影像技术， 2023 ， 39 （ 8 ）： 1160 - 1164 . DOI： 10.13929/j.issn.1003-3289.2023.08.009 http://dx.doi.org/10.13929/j.issn.1003-3289.2023.08.009 .

ZHANG J ， LI X ， LIU J ， et al . Stratified strain technique for evaluation on left ventricular myocardial function in rats intervened with doxorubicin ［J］. Chin J Med Imag Technol ， 2023 ， 39 （ 8 ）： 1160 - 1164 . DOI： 10.13929/j.issn.1003-3289.2023.08.009 http://dx.doi.org/10.13929/j.issn.1003-3289.2023.08.009 .

王冬妮，曹军英，吴璐璐，等 . 二维斑点追踪成像评价低温条件下兔左心室收缩功能改变［J］. 第三军医大学学报， 2020 ， 42 （ 11 ）： 1086 - 1090 . DOI： 10.16016/j.1000-5404.201912187 http://dx.doi.org/10.16016/j.1000-5404.201912187 .

WANG D N ， CAO J Y ， WU L L ， et al . Evaluation of rabbit left ventricular systolic function at low temperature by two-dimensional speckle-tracking echocardiography ［J］. J Third Mil Med Univ ， 2020 ， 42 （ 11 ）： 1086 - 1090 . DOI： 10.16016/j.1000-5404.201912187 http://dx.doi.org/10.16016/j.1000-5404.201912187 .

YE N ， JARDINE M J ， OSHIMA M ， et al . Blood pressure effects of canagliflozin and clinical outcomes in type 2 diabetes and chronic kidney disease： insights from the CREDENCE trial ［J］. Circulation ， 2021 ， 143 （ 18 ）： 1735 - 1749 . DOI： 10.1161/CIRCULATIONAHA.120.048740 http://dx.doi.org/10.1161/CIRCULATIONAHA.120.048740 .

CHEN Z G ， LI G G ， HUANG J ， et al . Subclinical impairment of left ventricular myocardium function in type 2 diabetes mellitus patients with or without hypertension ［J］. World J Diabetes ， 2024 ， 15 （ 6 ）： 1272 - 1279 . DOI： 10.4239/wjd.v15.i6.1272 http://dx.doi.org/10.4239/wjd.v15.i6.1272 .

GUPTA R ， MAITZ T ， EGELER D ， et al . SGLT2 inhibitors in hypertension： Role beyond diabetes and heart failure ［J］. Trends Cardiovasc Med ， 2023 ， 33 （ 8 ）： 479 - 486 . DOI： 10.1016/j.tcm.2022.05.005 http://dx.doi.org/10.1016/j.tcm.2022.05.005 .

KARIO K ， FERDINAND K C ， VONGPATANASIN W . Are SGLT2 inhibitors new hypertension drugs？［J］. Circulation ， 2021 ， 143 （ 18 ）： 1750 - 1753 . DOI： 10.1161/CIRCULATIONAHA.121.053709 http://dx.doi.org/10.1161/CIRCULATIONAHA.121.053709 .

徐叔云 . 药理实验方法学［Z］. 安徽医科大学. 1997

XU S Y . Pharmacological experimental methodology ［Z］. Anhui Medical University. 1997

ROTH G A ， MENSAH G A ， JOHNSON C O ， et al . Global burden of cardiovascular diseases and risk factors， 1990-2019： update from the GBD 2019 study ［J］. J Am Coll Cardiol ， 2020 ， 76 （ 25 ）： 2982 - 3021 . DOI： 10.1016/j.jacc.2020.11.010 http://dx.doi.org/10.1016/j.jacc.2020.11.010 .

WEBER K T . Fibrosis and hypertensive heart disease ［J］. Curr Opin Cardiol ， 2000 ， 15 （ 4 ）： 264 - 272 . DOI： 10.1097/00001573-200007000-00010 http://dx.doi.org/10.1097/00001573-200007000-00010 .

FRANGOGIANNIS N G . Cardiac fibrosis： Cell biological mechanisms， molecular pathways and therapeutic opportunities ［J］. Mol Aspects Med ， 2019 ， 65 ： 70 - 99 . DOI： 10.1016/j.mam.2018.07.001 http://dx.doi.org/10.1016/j.mam.2018.07.001 .

邢雨蒙，史静，颜彦，等 . 二维斑点追踪成像技术评价冠状动脉慢血流患者左室心肌分层应变［J］. 复旦学报（医学版）， 2018 ， 45 （ 4 ）： 467 - 472 . DOI： 10.3969/j.issn.1672-8467.2018.04.005 http://dx.doi.org/10.3969/j.issn.1672-8467.2018.04.005 .

XING Y M ， SHI J ， YAN Y ， et al . Assessment of left ventricular layer-specific myocardial strain in patients with coronary slow flow by two-dimensional speckle tracking echocardiography ［J］. Fudan Univ J Med Sci ， 2018 ， 45 （ 4 ）： 467 - 472 . DOI： 10.3969/j.issn.1672-8467.2018.04.005 http://dx.doi.org/10.3969/j.issn.1672-8467.2018.04.005 .

王瑞琪，康春松 . 二维分层应变技术评价高血压患者左心室心肌力学改变［J］. 中国临床医学影像杂志， 2019 ， 30 （ 9 ）： 633 - 636 . DOI： 10.12117/jccmi.2019.09.007 http://dx.doi.org/10.12117/jccmi.2019.09.007 .

WANG R Q ， KANG C S . Evaluation of left ventricular myocardial strain in patients with hypertension by two-dimensional strain echocardiography ［J］. J China Clin Med Imag ， 2019 ， 30 （ 9 ）： 633 - 636 . DOI： 10.12117/jccmi.2019.09.007 http://dx.doi.org/10.12117/jccmi.2019.09.007 .

SOUFI TALEB BENDIAB N ， MEZIANE-TANI A ， OUABDESSELAM S ， et al . Factors associated with global longitudinal strain decline in hypertensive patients with normal left ventricular ejection fraction ［J］. Eur J Prev Cardiol ， 2017 ， 24 （ 14 ）： 1463 - 1472 . DOI： 10.1177/2047487317721644 http://dx.doi.org/10.1177/2047487317721644 .

CASTOLDI G ， CARLETTI R ， IPPOLITO S ， et al . Cardioprotective effects of sodium glucose cotransporter 2 inhibition in angiotensin II-dependent hypertension are mediated by the local reduction of sympathetic activity and inflammation ［J］. Int J Mol Sci ， 2023 ， 24 （ 13 ）： 10710 . DOI： 10.3390/ijms241310710 http://dx.doi.org/10.3390/ijms241310710 .

HE L L ， MA S ， ZUO Q J ， et al . An effective sodium-dependent glucose transporter 2 inhibition， canagliflozin， prevents development of hypertensive heart failure in dahl salt-sensitive rats ［J］. Front Pharmacol ， 2022 ， 13 ： 856386 . DOI： 10.3389/fphar.2022.856386 http://dx.doi.org/10.3389/fphar.2022.856386 .

WEBER M A ， MANSFIELD T A ， CAIN V A ， et al . Blood pressure and glycaemic effects of dapagliflozin versus placebo in patients with type 2 diabetes on combination antihypertensive therapy： a randomised， double-blind， placebo-controlled， phase 3 study ［J］. Lancet Diabetes Endocrinol ， 2016 ， 4 （ 3 ）： 211 - 220 . DOI： 10.1016/S2213-8587（15）00417-9 http://dx.doi.org/10.1016/S2213-8587（15）00417-9 .

CASTRO P C ， SANTOS-RIOS T M ， MARTINS F L ， et al . Renal upregulation of NCC counteracts empagliflozin-mediated NHE3 inhibition in normotensive but not in hypertensive male rat ［J］. Am J Physiol Cell Physiol ， 2024 ， 326 （ 6 ）： C1573 - C1589 . DOI： 10.1152/ajpcell.00351.2023 http://dx.doi.org/10.1152/ajpcell.00351.2023 .

RAJASEKERAN H ， REICH H N ， HLADUNEWICH M A ， et al . Dapagliflozin in focal segmental glomerulosclerosis： a combined human-rodent pilot study ［J］. Am J Physiol Renal Physiol ， 2018 ， 314 （ 3 ）： F412 - F422 . DOI： 10.1152/ajprenal.00445.2017 http://dx.doi.org/10.1152/ajprenal.00445.2017 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Construction of a risk prediction model of mild cognitive impairment in hospitalized patients with hypertension

Correlation of arteriolar hyalinosis and clinicopathological features in patients with IgA nephropathy and hypertension

Correlation of morning blood pressure surge with severity of coronary artery lesions in essential hypertension patients with or without type 2 diabetes mellitus

Correlation of blood pressure circadian rhythm and blood pressure variability with carotid atherosclerosis in type 2 diabetes mellitus patients with hypertension

Myocardial protective effect of propofol postconditioning in renal hypertensive rats

Related Author

WANG Li1

ZHOU Lian2

YANG Yanni1 1School of Nursing

SHEN Yunzhu

XIONG Jiachuan

ZHAO Jinghong

Wang Yudong

Li Chuanwei

Related Institution

Department of Cardiology, First Affiliated Hospital, Army Medical University (Third Military Medical University)

Department of Nephrology, PLA Center for Nephrology, Chongqing Key Laboratory for Prevention and Treatment of Chronic Kidney Disease, Chongqing Clinical Research Center of Kidney and Urology Diseases, Second Affiliated Hospital, Army Medical University (Third Military Medical University)

Department of Cardiology, Chongqing Institute of Cardiovascular Diseases, Institute of Surgery Research, Daping Hospital, Third Military Medical University

Department of Endocrinology, Southwest Hospital, Third Military Medical University

Department of Anesthesiology, Affiliated Yongchuan Hospital of Chongqing Medical University

⁰