Pharmacological postconditioning with atorvastatin calcium attenuates myocardial ischemia/reperfusion injury in diabetic rats by phosphorylating GSK3β

被引：38

作者：

Chen, Linyan ^{[1
,2
]}

Cai, Ping ^{[1
,2
]}

Cheng, Zhendong ^{[1
,2
]}

Zhang, Zaibao ^{[1
,2
]}

Fang, Jun ^{[1
,2
]}

机构：

[1] Fujian Med Univ, Union Hosp, Dept Cardiol, 29 Xin Quan Rd, Fuzhou 350001, Fujian, Peoples R China

[2] Fujian Inst Coronary Heart Dis, Fuzhou 350001, Fujian, Peoples R China

来源：

EXPERIMENTAL AND THERAPEUTIC MEDICINE | 2017年 / 14卷 / 01期

关键词：

atorvastatin calcium; myocardium; ischemia/reperfusion injury; type; 2; diabetes; glycogen synthase kinase 3 beta; ISCHEMIA-REPERFUSION INJURY; GLYCOGEN-SYNTHASE KINASE-3; INFARCT SIZE; DIMETHYL-SULFOXIDE; IN-VIVO; SHORT-TERM; DIMETHYLSULFOXIDE; HEART; CARDIOPROTECTION; HEAT-SHOCK-PROTEIN-70;

D O I：

10.3892/etm.2017.4457

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

Diabetes is an independent risk factor for myocardial ischemia, and many epidemiological data and laboratory studies have revealed that diabetes significantly exacerbated myocardial ischemia/reperfusion injury and ameliorated protective effects. The present study aimed to determine whether pharmacological postconditioning with atorvastatin calcium lessened diabetic myocardial ischemia/reperfusion injury, and investigated the role of glycogen synthase kinase (GSK beta) in this. A total of 72 streptozotocin-induced diabetic rats were randomly divided into six groups, and 24 age-matched male non-diabetic Sprague-Dawley rats were randomly divided into two groups. Rats all received 40 min myocardial ischemia followed by 180 min reperfusion, except sham-operated groups. Compared with the non-diabetic ischemia/reperfusion model group, the diabetic ischemia/reperfusion group had a comparable myocardial infarct size, but a higher level of serum cardiac troponin I (cTnI) and morphological alterations to their myocardial cells. Compared with the diabetic ischemia/reperfusion group, the group that received pharmacological postconditioning with atorvastatin calcium had smaller myocardial infarct sizes, lower levels of cTnI, reduced morphological alterations to myocardial cells, higher levels of p-GSK3 beta, heat shock factor (HSF)-1 and heat shock protein (HSP)70. The cardioprotective effect conferred by atorvastatin calcium did not attenuate myocardial ischemia/reperfusion injury following application of TDZD-8, which phosphorylates and inactivates GSK beta. Pharmacological postconditioning with atorvastatin calcium may attenuate diabetic heart ischemia/reperfusion injury in the current context. The phosphorylation of GSK3 beta serves a critical role during the cardioprotection in diabetic rats, and p-GSK3 beta may accelerate HSP70 production partially by activating HSF-1 during myocardial ischemic/reperfusion injury.

引用

页码：25 / 34

页数：10

共 65 条

[1]

Stress (heat shock) proteins - Molecular chaperones in cardiovascular biology and disease [J].

Benjamin, IJ ;

McMillan, DR .

CIRCULATION RESEARCH, 1998, 83 (02) :117-132

[2]

Prostaglandins mediate the cardioprotective effects of atorvastatin against ischemia-reperfusion injury [J].

Birnbaum, Y ;

Ye, YM ;

Rosanio, S ;

Tavackoli, S ;

Hu, ZY ;

Schwarz, ER ;

Uretsky, BF .

CARDIOVASCULAR RESEARCH, 2005, 65 (02) :345-355

[3]

Activation of estrogen receptor-α protects the in vivo rabbit heart from ischemia-reperfusion injury [J].

Booth, EA ;

Obeid, NR ;

Lucchesi, BR .

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2005, 289 (05) :H2039-H2047

[4]

Low-pressure reperfusion alters mitochondrial permeability transition [J].

Bopassa, JC ;

Michel, P ;

Gateau-Roesch, O ;

Ovize, M ;

Ferrera, R .

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2005, 288 (06) :H2750-H2755

[5]

Management of intracoronary thrombosis complicating percutaneous transluminal coronary angioplasty [J].

Boston, DR ;

Malouf, A ;

Barry, WH .

CLINICAL CARDIOLOGY, 1996, 19 (07) :536-542

[6]

GSK3 inhibitors: Development and therapeutic potential [J].

Cohen, P ;

Goedert, M .

NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (06) :479-487

[7]

Collins R, 2002, LANCET, V360, P7, DOI 10.1016/S0140-6736(02)09327-3

[8]

Engineered apyrase averts clot formation [J].

Crunkhorn, Sarah .

NATURE REVIEWS DRUG DISCOVERY, 2014, 13 (10) :724-725

[9]

Cyclosporine before PCI in Patients with Acute Myocardial Infarction [J].

Cung, T. -T. ;

Morel, O. ;

Cayla, G. ;

Rioufol, G. ;

Garcia-Dorado, D. ;

Angoulvant, D. ;

Bonnefoy-Cudraz, E. ;

Guérin, P. ;

Elbaz, M. ;

Delarche, N. ;

Coste, P. ;

Vanzetto, G. ;

Metge, M. ;

Aupetit, J. -F. ;

Jouve, B. ;

Motreff, P. ;

Tron, C. ;

Labeque, J. -N. ;

Steg, P. G. ;

Cottin, Y. ;

Range, G. ;

Clerc, J. ;

Claeys, M. J. ;

Coussement, P. ;

Prunier, F. ;

Moulin, F. ;

Roth, O. ;

Belle, L. ;

Dubois, P. ;

Barragan, P. ;

Gilard, M. ;

Piot, C. ;

Colin, P. ;

De Poli, F. ;

Morice, M. -C. ;

Ider, O. ;

Dubois-Rande, J. -L. ;

Unterseeh, T. ;

Le Breton, H. ;

Beard, T. ;

Blanchard, D. ;

Grollier, G. ;

Malquarti, V. ;

Staat, P. ;

Sudre, A. ;

Elmer, E. ;

Hansson, M. J. ;

Bergerot, C. ;

Boussaha, I. ;

Jossan, C. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (11) :1021-1031

[10]

DELATORRE JC, 1983, ANN NY ACAD SCI, V411, P293

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