Protective Effects of Kaempferol against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart via Antioxidant Activity and Inhibition of Glycogen Synthase Kinase-3β

被引:115
作者
Zhou, Mingjie [1 ,2 ]
Ren, Huanhuan [3 ]
Han, Jichun [3 ]
Wang, Wenjuan [3 ]
Zheng, Qiusheng [3 ,4 ]
Wang, Dong [1 ]
机构
[1] Shandong Prov Qianfoshan Hosp, Jinan 250014, Peoples R China
[2] Weifang Med Univ, Weifang 261031, Peoples R China
[3] Binzhou Med Univ, Yantai 264003, Peoples R China
[4] Shihezi Univ, Sch Pharm, Shihezi 832002, Peoples R China
关键词
PERMEABILITY TRANSITION PORE; THERAPEUTIC TARGET; CARDIAC MITOCHONDRIA; FREE-RADICALS; KINASE; REPERFUSION; APOPTOSIS; ALPHA;
D O I
10.1155/2015/481405
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Objective. This study aimed to evaluate the protective effect of kaempferol against myocardial ischemia/reperfusion (I/R) injury in rats. Method. Left ventricular developed pressure (LVDP) and its maximum up/down rate (+/-dp/dt(max)) were recorded as myocardial function. Infarct size was detected with 2,3,5-triphenyltetrazolium chloride staining. Cardiomyocyte apoptosis was determined using terminal deoxynucleotidyl nick-end labeling (TUNEL). The levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione/glutathione disulfide (GSH/GSSG) ratio, and tumor necrosis factor-alpha (TNF-alpha) were determined using enzyme linked immunosorbent assay (ELISA). Moreover, total glycogen synthase kinase-3 beta (GSK-3 beta), phospho-GSK-3 beta (P-GSK-3 beta), precaspase-3, cleaved caspase-3, and cytoplasm cytochrome C were assayed using Western blot analysis. Results. Pretreatment with kaempferol significantly improved the recovery of LVDP and +/-dp/dt(max), as well as increased the levels of SOD and P-GSK-3 beta and GSH/GSSG ratio. However, the pretreatment reduced myocardial infarct size and TUNEL-positive cell rate, as well as decreased the levels of cleaved caspase-3, cytoplasm cytochrome C, CK, LDH, MDA, and TNF-alpha. Conclusion. These results suggested that kaempferol provides cardioprotection via antioxidant activity and inhibition of GSK-3 beta activity in rats with I/R.
引用
收藏
页数:8
相关论文
共 34 条
[1]   Glycogen synthase kinase-3: Properties, functions, and regulation [J].
Ali, A ;
Hoeflich, KP ;
Woodgett, JR .
CHEMICAL REVIEWS, 2001, 101 (08) :2527-2540
[2]  
[Anonymous], 2014, Oxidative Medicine and Cellular Longevity, DOI DOI 10.1155/2014/376515
[3]   Inhibition of mitochondrial permeability transition prevents mitochondrial dysfunction, cytochrome c release and apoptosis induced by heart ischemia [J].
Borutaite, V ;
Jekabsone, A ;
Morkuniene, R ;
Brown, GC .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2003, 35 (04) :357-366
[4]   Tumor necrosis factor-α and interleukin-1β synergistically depress human myocardial function [J].
Cain, BS ;
Meldrum, DR ;
Dinarello, CA ;
Meng, XZ ;
Joo, KS ;
Banerjee, A ;
Harken, AH .
CRITICAL CARE MEDICINE, 1999, 27 (07) :1309-1318
[5]   Inhibition of glycogen synthase kinase-3β attenuates the development of carrageenan-induced lung injury in mice [J].
Cuzzocrea, S. ;
Crisafulli, C. ;
Mazzon, E. ;
Esposito, E. ;
Muia, C. ;
Abdelrahman, M. ;
Di Paola, R. ;
Thiemermann, C. .
BRITISH JOURNAL OF PHARMACOLOGY, 2006, 149 (06) :687-702
[6]   Free radicals in the physiological control of cell function [J].
Dröge, W .
PHYSIOLOGICAL REVIEWS, 2002, 82 (01) :47-95
[7]   Isoflurane postconditioning prevents opening of the mitochondrial permeability transition pore through inhibition of glycogen synthase kinase 3β [J].
Feng, JH ;
Lucchinetti, E ;
Ahuja, P ;
Pasch, T ;
Perriard, JC ;
Zaugg, M .
ANESTHESIOLOGY, 2005, 103 (05) :987-995
[8]   Glycogen synthase kinase 3 inhibition protects the heart from acute ischemia-reperfusion injury via inhibition of inflammation and apoptosis [J].
Gao, Hao-Kao ;
Yin, Zhong ;
Zhou, Ning ;
Feng, Xu-Yang ;
Gao, Feng ;
Wang, Hai-Chang .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2008, 52 (03) :286-292
[9]   A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer [J].
Gates, Margaret A. ;
Tworoger, Shelley S. ;
Hecht, Jonathan L. ;
De Vivo, Immaculata ;
Rosner, Bernard ;
Hankinson, Susan E. .
INTERNATIONAL JOURNAL OF CANCER, 2007, 121 (10) :2225-2232
[10]   Historical Perspective on the Pathology of Myocardial Ischemia/Reperfusion Injury [J].
Jennings, Robert B. .
CIRCULATION RESEARCH, 2013, 113 (04) :428-438