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| Effect of dihydroquercetin on the phosphoinositide-3-kinaset/glycogen synthase kinase-3β signaling pathway in the myocardium of rats with acute myocardial ischemia induced by isoproterenol |
| WU Mingjuan1 FEI Hongxin2 TIAN Ming3 ZHOU Zhongguang3 HAN Yusheng4 |
1.Heilongjiang Academy of Chinese Medicine, Heilongjiang Province, Harbin 150036, China;
2.Department of Basic Medicine, Guangxi University of Science and Technology, Guangxi Zhuang Autonomous Region, Liuzhou 545005, China;
3.Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Heilongjiang Province, Harbin 150040, China;
4.Experiment Center, Heilongjiang University of Chinese Medicine, Heilongjiang Province, Harbin 150040, China |
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Abstract Objective To explore the effect of dihydroquercetin on the phosphoinositide-3-kinaset (PI3K)/glycogen synthase kinase-3β (GSK-3β) signaling pathway in the myocardium of rats with acute myocardial ischemia induced by isoproterenol. Methods Sixty clean SD rats were randomly divided into blank group, model group, Di′ao Xinxuekang group, high dose (60 mg/kg) of dihydroquercetin group, medium dose (30 mg/kg) of dihydroquercetin group, low dose (15 mg/kg) of dihydroquercetin group by random number table method. The drug was administered by continuous gavage for 14 d. The rat models of acute myocardial ischemia were established with intraperitoneal injection of isoproterenol from day 12. The hemorheology was observed, the levels of creatine kinase (CK), lactate dehydrogenase (LDH), nitric oxide (NO) in rat serum and the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malonaldehyde (MDA) in rat myocardium were measured; the protein expression levels of PI3K, phosphorylation protein kinase B (PKB) and GSK-3β in rat myocardium were detected by Western blot. Results Compared with the blank group, the whole blood viscosity, plasma viscosity, haematocrit was significantly increased in model group (P ＜ 0.05), serum CK and LDH levels increased (P ＜ 0.05), NO level decreased (P ＜ 0.05), the myocardial SOD, GSH-Px, CAT level and the protein expression of PI3K were reduced (P ＜ 0.05), MDA level and the protein expression of GSK-3β were increased (P ＜ 0.05). Compared with the model group, the levels of plasma viscosity in high, medium, low dose of dihydroquercetin group decreased (P ＜ 0.05), the haematocrit in medium, low dose of dihydroquercetin group decreased (P ＜ 0.05), and the levels of serum LDH and CK in high, medium dose of dihydroquercetin group decreased (P ＜ 0.05), NO level in each dose of dihydroquercetin group was increased (P ＜ 0.05), the SOD, GSH-Px, CAT level and the protein expression of PI3K were increased in each dose of dihydroquercetin group (P ＜ 0.05), the myocardial MDA level was reduced (P ＜ 0.05), and the protein expression of GSK-3β in high, medium dose of dihydroquercetin group decreased (P ＜ 0.05). Conclusion Dihydroquercetin can inhibit oxidative stress cascade, regulate myocardial blood flow, block the progress of myocardial ischemia in rats with acute myocardial ischemia through regulating PI3K/GSK-3β signaling pathway, so as to play an anti-myocardial ischemia role.
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[1] Yang G，Wang Y，Zeng Y，et al. Rapid health transition in China，1990-2010：findings from the Global Burden of Disease Study 2010 [J]. Lancet，2013，9882（9882）：1987-2015.
[2] 孙治霞，索红亮，王丽辉，等.五参顺脉胶囊通过抑制内质网应激诱导的凋亡减轻大鼠冠脉侵入性损伤[J].中国病理生理杂志，2018，34（10）：1790-1795.
[3] 王秋红，匡海学，吴伦，等.二氢槲皮素对异丙肾上腺素致大鼠心肌缺血的保护作用[J].中国实验方剂学杂志，2011，17（17）：177-180.
[4] 王知斌，翟亚东，苏晓琳，等.二氢槲皮素对H2O2诱导H9c2心肌细胞损伤的保护作用[J].中医药信息，2014， 31（4）：16-19.
[5] Sun X，Chen ＲC，Yang ZH，et al. Taxifolin prevents diabetic cardiomyopathy in vivo and in vitro by inhibition of oxidative stress and cell apoptosis [J]. Food Chem Toxicol，2014，63：221-232.
[6] 卢宁，韩吉春，任博雪，等.二氢槲皮素预处理对心肌缺血/再灌注损伤抗氧化作用的影响[J].中国药理学通报，2017，33（4）：487-492.
[7] Rawlings N，Lee L，Nakamura Y，et al. Protective role of the deSUMOylating enzyme SENP3 in myocardial ischemia-reperfusion injury [J]. PLoS One，2019，14（4）：e0213331.
[8] Kohlhauer M，Pell VR，Burger N，et al. Protection against cardiac ischemia-reperfusion injury by hypothermia and by inhibition of succinate accumulation and oxidation is additive [J]. Basic Res Cardiol，2019，114（3）：18.
[9] Wu TK，Chen CH，Pan YR，et al. Cetrimonium Bromide Inhibits Cell Migration and Invasion of Human Hepatic SK-HEP-1 Cells Through Modulating the Canonical and Non-canonical TGF-β Signaling Pathways [J]. Anticancer Res，2019，39（7）：3621-3631.
[10] Wu YY，Wu HC，Wu JE，et al. The dual PI3K/mTOR inhibitor BEZ235 restricts the growth of lung cancer tumors regardless of EGFR status，as a potent accompanist in combined therapeutic regimens [J]. J Exp Clin Cancer，2019，38（1）：282.
[11] Jia L，Hu Y，Yang G，et al. Puerarin suppresses cell growth and migration in HPV-positive cervical cancer cells by inhibiting the PI3K/mTOR signaling pathway [J]. Exp Ther Med，2019，18（1）：543-549.
[12] Ohashi E，Kohno K，Arai N，et al. Adenosine N1-Oxide Exerts Anti-inflammatory Effects through the PI3K/Akt/GSK-3β Signaling Pathway and Promotes Osteogenic and Adipocyte Differentiation [J]. Biol Pharm Bull，2019， 42（6）：968-976.
[13] Li C，Tang B，Feng Y，et al. Pinostrobin Exerts Neuroprotective Actions in Neurotoxin-Induced Parkinson's Disease Models through Nrf2 Induction [J]. J Agric Food Chem，2018，66（31）：8307-8318.
[14] Chen X，Wei R，Jin T，et al. Notoginsenoside R1 alleviates TNF-α-induced pancreatic β-cell Min6 apoptosis and dysfunction through up-regulation of miR-29a [J]. Artif Cells Nanomed Biotechnol，2019，47（1）：2379-2388.
[15] Song Y，Cui X，Zhao R，et al. Emodin protects against lipopolysaccharide-induced inflammatory injury in HaCaT cells through upregulation of miR-21 [J]. Artif Cells Nanomed Biotechnol，2019，47（1）：2654-2661.
[16] Sun Q，Jia N，Li X，et al. Grape seed proanthocyanidins ameliorate neuronal oxidative damage by inhibiting GSK-3β-dependent mitochondrial permeability transition pore opening in an experimental model of sporadic Alzheimer′s disease [J]. Aging（Albany NY），2019，11（12）：4107-4124.
[17] Li L，Sha Z，Wang Y，et al. Pre-treatment with a combination of Shenmai and Danshen injection protects cardiomyocytes against hypoxia/reoxygenation- and H2O2-induced injury by inhibiting mitochondrial permeability transition pore opening [J]. Exp Ther Med，2019，17（6）：4643-4652.
[18] Rai SN，Dilnashin H，Birla H，et al. The Role of PI3K/Akt and ERK in Neurodegenerative Disorders [J]. Neurotox Res，2019，35（3）：775-795.
[19] Bhurtel S，Katila N，Srivastav S，et al. Mechanistic comparison between MPTP and rotenone neurotoxicity in mice [J]. Neurotoxicology，2019，71：113-121.
[20] Zhou LJ，Mo YB，Bu X，et al. Erinacine Facilitates the Opening of the Mitochondrial Permeability Transition Pore Through the Inhibition of the PI3K/ Akt/GSK-3β Signaling Pathway in Human Hepatocellular Carcinoma [J]. Cell Physiol Biochem，2018，50（3）：851-867. |
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