Heart protective effects and mechanism of quercetin preconditioning on anti-myocardial ischemia reperfusion (IR) injuries in rats.
In this study, we investigated the effects and mechanism of quercetin preconditioning on anti-myocardial ischemia reperfusion (IR) injuries in vivo. Meanwhile, their potential anti-oxidative stress and anti-inflammation effect were assessed. SD rats were orally given quercetin 250 mg/kg. Myocardium apoptosis was determined with TUNEL staining. The biomarkers related to myocardial ischemia injury were determined. Simultaneously, hemodynamic parameters were monitored as left ventricular systolic pressure (LVSP), LV end-diastolic pressure (LVEDP) and maximal rate of increase and decrease of left ventricular pressure (dP/dtmax). The oxidative stress indicators and inflammatory factors were also evaluated. Western blot method was used for analysis of PI3K, Akt, p-Akt, Bax and Bcl-2 protein expressions. The results showed that quercetin significantly reduced apoptosis rate, improved cardiac function, decreased levels of creatine kinase (CK), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH). Quercetin also restrained the oxidative stress related to myocardial ischemia injury as evidenced by decreased malondialdehyde (MDA), and elevated GSH, superoxide dismutase (SOD), catalase (CAT), glutathione-peroxidase (GSH-Px), glutathione reductase (GR) activity. Meanwhile, the inflammatory cascade was inhibited as evidenced by decreased cytokines such as tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and interleukin-1β (IL-1β). Our results still showed that quercetin pretreatment significantly inhibited the apoptosis by decreasing the number of apoptotic cells, decreasing the level of cleaved Bax, and increasing the level of Bcl-2 in rats subjected to I/R injury. Simultaneously, quercetin pretreatment markedly increased the phosphorylation of Akt. Blockade of PI3K activity by LY294002, dramatically abolished its anti-apoptotic effect and lowered Akt phosphorylation level. It can be concluded that quercetin pretreatment was protected against myocardium IR injury by decreasing oxidative stress, repressing inflammatory cascade, inhibiting apoptosis in vivo and PI3K/Akt pathway involved in the anti-apoptotic effect.
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
Hui
H
Liu
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
Xiaolan
X
Guo
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
Yi
Y
Chu
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China. Electronic address: spluxy@126.com.
Shaoping
S
Lu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D002097:C-Reactive Protein; D002316:Cardiotonic Agents; D002374:Catalase; D002867:Chromones; D003402:Creatine Kinase; D004791:Enzyme Inhibitors; D005979:Glutathione Peroxidase; D007770:L-Lactate Dehydrogenase; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D011794:Quercetin; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; C494828:Bax protein, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Antioxidant; Myocardial ischemia reperfusion; PI3K/Akt pathway; Quercetin