[1]栗志勇,张 慧,张 婷,等.丹皮酚对急性心肌梗死大鼠氧化应激和内皮型一氧化氮合酶信号通路的影响[J].新乡医学院学报,2017,34(5):356-360.[doi:10.7683/xxyxyxb.2017.05.003]
 LI Zhi-yong,ZHANG Hui,ZHANG Ting,et al.Effect of paeonol preconditioning on oxidative stress and endothelial nitric oxide synthase signal pathway in rats with acute myocardial infarction[J].Journal of Xinxiang Medical University,2017,34(5):356-360.[doi:10.7683/xxyxyxb.2017.05.003]
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丹皮酚对急性心肌梗死大鼠氧化应激和内皮型一氧化氮合酶信号通路的影响
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
34
期数:
2017年5
页码:
356-360
栏目:
基础研究
出版日期:
2017-05-05

文章信息/Info

Title:
Effect of paeonol preconditioning on oxidative stress and endothelial nitric oxide synthase signal pathway in rats with acute myocardial infarction
作者:
栗志勇1张 慧2张 婷3宋 宇2
(1.安阳市第三人民医院胸外科,河南 安阳 455000;2.新乡医学院药学院药理学教研室,河南 新乡 453003;3.新乡医学院三全学院遗传与基因工程教研室,河南 新乡 453003)
Author(s):
LI Zhi-yong1ZHANG Hui2ZHANG Ting3SONG Yu2
(1.Department of Thoracic Surgery,the Third People′s Hospital of Anyang City,Anyang 455000,Henan Province,China;2.Department of Pharmacology,College of Pharmacy,Xinxiang Medical University,Xingxiang 453003,Henan Province,China;3.Department of Heredity and Genetic Engineering,Sanquan Medical College,Xinxiang Medical University,Xingxiang 453003,Henan Province,China)
关键词:
丹皮酚急性心肌梗死心肌酶内皮型一氧化氮合酶氧化应激
Keywords:
paeonolacute myocardial infarctioncardiac marker enzymeendothelial nitric oxide synthaseoxidative stress
分类号:
R965
DOI:
10.7683/xxyxyxb.2017.05.003
文献标志码:
A
摘要:
目的 观察丹皮酚对急性心肌梗死模型大鼠心脏的保护作用,并探讨可能的分子机制。方法 将50只大鼠随机分为对照组、模型组及丹皮酚低、中、高剂量组,每组10只。丹皮酚低、中、高剂量组大鼠分别腹腔注射丹皮酚注射液4、8、16 mg·kg-1·d-1。对照组、模型组大鼠腹腔注射生理盐水1.6 mL·kg-1·d-1,连续给药14 d。末次给药后30 min,除对照组大鼠外,其余各组大鼠均通过永久性结扎大鼠左冠状动脉前降支制作急性心肌梗死模型。并于冠状动脉结扎后6 h,检测血浆肌酸激酶(CK)、肌酸激酶同工酶(CKMB)、乳酸脱氢酶(LDH)、心肌肌钙蛋白T(cTnT)、一氧化氮(NO)、8-异前列腺素水平,及心肌组织中丙二醛(MDA)和超氧化物歧化酶(SOD)水平,同时实时定量反转录-聚合酶链式反应检测心肌组织中内皮型一氧化氮合酶(eNOS)mRNA表达。结果 与对照组比较,模型组及丹皮酚低、中、高剂量组大鼠心电图中ST段显著升高(P<0.01),血浆中CK、CKMB、LDH、cTnT及心肌组织中MDA水平均显著增高(P<0.05),而血浆中NO含量、SOD活力和心肌组织中eNOS mRNA表达水平显著降低(P<0.05)。与模型组比较,丹皮酚中、高剂量组大鼠心电图中ST段显著降低(P<0.05),血浆中CK、CKMB、LDH、cTnT、8-异前列腺素和心肌组织中MDA水平显著下降(P<0.05),同时血浆中NO含量和心肌组织中SOD活性、eNOS mRNA表达显著增加(P<0.05);丹皮酚低剂量组与模型组大鼠比较,除CKMB显著下降外(P<0.05),其余均无明显变化(P>0.05)。与丹皮酚低剂量组比较,丹皮酚高剂量组大鼠心电图中ST段显著降低(P<0.05),血浆中CK、CKMB、LDH、cTnT、8-异前列腺素及心肌组织中MDA水平显著降低(P<0.05),而血浆中NO含量、SOD活力和心肌组织中eNOS mRNA表达显著增高(P<0.05);丹皮酚中剂量组与低剂量组大鼠比较,除LDH、cTnT、SOD活力、8-异前列腺素外,其余指标均有显著变化(P<0.05)。与丹皮酚中剂量组比较,丹皮酚高剂量组大鼠心电图中ST段显著降低(P<0.05),血浆中CK、CKMB、LDH、cTnT、8-异前列腺素及心肌组织中MDA水平显著降低(P<0.05),心肌组织中eNOS mRNA表达显著升高(P<0.05),而血浆中NO含量和心肌组织中SOD活力变化不明显(P>0.05)。结论 丹皮酚对急性心肌梗死大鼠心肌具有保护作用,其作用可能与激活eNOS信号系统和抑制氧化应激有关。
Abstract:
Objective To observe the cardioprotective effect of paeonol in acute myocardial infarction rats and explore the potential molecular mechanisms of this effect.Methods Fifty rats were randomly divided into control group,model group,low dose paeonol group,middle dose paeonol group and high dose paeonol group,with 10 rats in each group.The rats in low dose paeonol group,middle dose paeonol group and high dose paeonol group were given paeonol injection intraperitoneally(4,8,16 mg·kg-1·d-1 respectively)for 14 days;the rats in the control group and the model group were injected saline(1.6 mL·kg-1·d-1) intraperitoneally for 14 days.The acute myocardial infarction model was established by occluding the left anterior descending artery permanently in all rats except control group at 30 min after the last administration.The levels of casein kinase(CK),isoenzyme of creatine kinase(CKMB),lactate dehydrogenase(LDH),cardiac troponin T(cTnT),nitric oxide(NO),8 isoprostane in plasma and malondialdehyde(MDA),superoxide dismutase(SOD)in myocardium were measured at 6 h after occluding the coronary artery.The expression of endothelial nitric oxide synthase(eNOS)mRNA were detected by quantitative real-time polymerase chain reaction.Results Compared with the control group,the ST segment elevated more significantly(P<0.01),the levels of CK,CKMB,LDH,cTnT,8-isoprostanes in plasma and MDA in myocardium increased more obviously in the model group,low dose paeonol group,middle dose paeonol group and high dose paeonol group(P<0.05);the NO content in plasma and SOD activity,the expression of eNOS mRNA in myocardium were markedly decreased(P<0.05).Compared with the model group,the ST segment depressed more significantly(P<0.05),the levels of CK,CKMB,LDH,cTnT,8-isoprostanes in plasma and MDA in myocardium decreased obviously in the medium dose paeonol group and high dose paeonol group(P<0.05);the NO content in plasma and SOD activity,the expression of eNOS mRNA in myocardium were significantly increased(P<0.05).The level of CKMB in plasma of rats in low dose paeonol group was significantly lower than that in the model group(P<0.05);there was no statistic difference in the other indexes between the low dose paeonol group and model group(P>0.05).Compared with the low dose paeonol group,the ST segment depressed more significantly(P<0.05),the levels of CK,CKMB,LDH,cTnT in plasma and MDA in myocardium decreased more obviously in the high dose paeonol group(P<0.05);the NO content in plasma and SOD activity,the expression of eNOS mRNA in myocardium were markedly increased(P<0.05).There was no significant changes in the levels of LDH,cTnT,8-isoprostanes and SOD activity between the low dose paeonol group and middle dose paeonol group(P>0.05),while the other indexes had significant changes(P<0.05).Compared with the middle dose paeonol group,the ST segment depressed more significantly(P<0.05),the levels of CK,CKMB,LDH,cTnT in plasma and MDA in myocardium decreased obviously in the high dose paeonol groups(P<0.05);the expression of eNOS mRNA in myocardium was obviously increased(P<0.05);there were no significant changes in NO content in plasma and SOD activity in myocardium between middle dose paeonol group and high dose paeonol group(P>0.05).Conclusion Paeonol has a protective effect on myocardium in rats with acute myocardial infarction.This effect may be relate with the activation of eNOS signal sysytem and inhibition of oxidative stress.

参考文献/References:

[1] LI J L,YANG Z,WU S,et al.Relationship between endothelial nitric oxide synthase,insulin resistance and macrovascular disease in patients with acute myocardial infarction[J].J Int Med Res,2012,40(2):687-693.
[2] ZHANG W,HAN Y,MENG G,et al.Direct renin inhibition with aliskiren protects against myocardial ischemia/reperfusion injury by activating nitric oxide synthase signaling in spontaneously hypertensive rats[J].J Am Heart Assoc,2014,3(1):e000606.
[3] WANG Y,HU Z,SUN B,et al.Ginsenoside Rg3 attenuates myocardial ischemia/ reperfusion injury via Akt/endothelial nitric oxidesynthase signaling and the B cell lymphoma/B cell lymphoma associated X protein pathway[J].Mol Med Rep,2015,11(6):4518-4524.
[4] ZIGRA A M,RALLIDIS L S,ANASTASIOU G,et al.eNOS gene variants and the risk of premature myocardial infarction[J].Dis Markers,2013,34(6):431-436.
[5] QIN W,CHEN X,LIU P.Inhibition of TGF-β1 by eNOS gene transfer provides cardiac protection after myocardial infarction[J].J Biomed Res,2010,24(2):145-152.
[6] JONES S P,GIROD W G,PALAZZO A J,et al.Myocardial ischemia reperfusion injury is exacerbated in absence of endothelial cell nitric oxide synthase[J].Am J Physiol,1999,276:H1567-H1573.
[7] SIDDIQUI A H,GULATI R,TAUHEED N,et al.Correlation of waist-to-hip ratio(WHR)and oxidative stress in patients of acute myocardial infarction(AMI)[J].J Clin Diagn Res,2014,8(1):4-7.
[8] BASHAR T,AKHTER N.Study on oxidative stress and antioxidant level in patients of acute myocardial infarction before and after regular treatment[J].Bangladesh Med Res Counc Bull,2014,40(2):79-84.
[9] CHEN H,XU Y,WANG J,et al.Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS,inflammation and oxidative stress in rat[J].Int J Clin Exp Pathol,2015,8(9):10139-10147.
[10] ZHU X Y,ZHANG Z L,LI P,et al.Shenyuan,an extract of American Ginseng and Corydalis Tuber formula,attenuates cardiomyocyte apoptosis via inhibition of endoplasmic reticulum stress and oxidative stress in a porcine model of acute myocardial infarction[J].J Ethnopharmacol,2013,150(2):672-681.
[11] ZHANG J Y,CAO Y X,WENG W L,et al.Paeonol induces vasodilatation in rat mesenteric artery via inhibiting extracellular Ca2+ influx and intracellular Ca2+ release[J].Chin J Integr Med,2013,19(7):510-516.
[12] 陆建洪,翟昌林,陈捷.丹皮酚对大鼠缺血再灌注损伤心肌细胞凋亡及其Bcl-2和Bax表达的影响[J].中国中医药科技,2013,20(2):151-152.
[13] 张金花,熊永爱.丹皮酚对大鼠缺血性心律失常及其心肌细胞 miRNA-1表达的影响[J].中国实验方剂学杂志,2015,21(5):129-132.
[14] GUO J,LI H Z,WANG L C,et al.Increased expression of calcium sensing receptors in atherosclerosis confers hypersensitivity to acute myocardial infarction in rats[J].Mol Cell Biochem,2012,366:345-354.
[15] MING X,TONGSHEN W,DELIN W,et al.Cardioprotective effect of the compound yangshen granule in rat models with acute myocardial infarction[J].Evid Based Complement Alternat Med,2012,2012:717123.
[16] CHEN C,DU P,WANG J.Paeoniflorin ameliorates acute myocardial infarction of rats by inhibiting inflammation and inducible nitricoxide synthase signaling pathways[J].Mol Med Rep,2015,12(3):3937-3943.
[17] 王思颖,李绍旦,刘毅.通心络对心肌梗死模型大鼠心肌损伤保护作用及机制的研究[J].环球中医药,2016,9(6):650-653.
[18] WOLFRUM S,DENDORFER A,SCHUTT M,et al.Simvastatin acutely reduces myocardial reperfusion injury in vivo by activating the phosphatidylinositide 3 kinase/Akt pathway[J].J Cardiovasc Pharmacol,2004,44:348-355.
[19] BERARD E.Metabolism and regulation of nitric oxide:a hard to control mediator[J].Arch Pediatr,2013,4407:1004-1011.
[20] AKSOY S,CAM N,GURKAN U,et al.Oxidative stress and severity of coronary artery disease in young smokers with acute myocardial infarction[J].Cardiol J,2012,19(4):381-386.
[21] NAKAMURA T,NISHI H,KOKUSENYA Y,et al.Mechanism of antioxidative activity of fluvastatin-determination of the active position[J].Chem Pharm Bull(Tokyo),2000,48(2):235-237.
[22] SALEHI I,MOHAMMADI M,MIRZAEI F,et al.Amlo dipine attenuates oxidative stress in the heart and blood of high cholesterol diet rabbits[J].Cardio Vasc J Afr,2012,23(1):18-22.

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更新日期/Last Update: 2017-05-05