[1]王 皓,王少学,李素敏,等.黄芪甲甙对急性心肌梗死大鼠早期心功能、炎性相关因子及内皮型一氧化氮合酶信号通路的影响[J].新乡医学院学报,2018,35(3):167-172.[doi:10.7683/xxyxyxb.2018.03.002]
 WANG Hao,WANG Shao-xue,LI Su-min,et al.Effect of astragaloside on cardiac function,inflammatory-related cytokines and endothelial nitric oxide synthase signaling pathway in rats with acute myocardial infarction[J].Journal of Xinxiang Medical University,2018,35(3):167-172.[doi:10.7683/xxyxyxb.2018.03.002]
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黄芪甲甙对急性心肌梗死大鼠早期心功能、炎性相关因子及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:
35
期数:
2018年3
页码:
167-172
栏目:
基础研究
出版日期:
2018-03-05

文章信息/Info

Title:
Effect of astragaloside on cardiac function,inflammatory-related cytokines and endothelial nitric oxide synthase signaling pathway in rats with acute myocardial infarction
作者:
王 皓12王少学2李素敏2韩东明1
(1.新乡医学院第一临床学院,河南 新乡 453003;2.原阳县人民医院超声科,河南 原阳 453500)
Author(s):
WANG Hao12WANG Shao-xue2LI Su-min2HAN Dong-ming1
(1.The First Clinical College of Xinxiang Medical University,Xingxiang 453003,Henan Province,China ;2.Department of Ultrasonography the People′s Hospital of Yuanyang County,Xinxiang 453500,Henan Province,China)
关键词:
黄芪甲甙急性心肌梗死Toll样受体内皮型一氧化氮合酶
Keywords:
astragalosideacute myocardial infarctiontoll-like receptorendothelial nitric oxide synthase
分类号:
R965
DOI:
10.7683/xxyxyxb.2018.03.002
文献标志码:
A
摘要:
目的 观察黄芪甲甙对急性心肌梗死模型大鼠心脏的保护作用,并探讨其可能的分子机制。方法 将45只Wistar大鼠随机分为假手术组、模型组和黄芪甲甙组,每组15只。模型组和黄芪甲甙组大鼠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,假手术组大鼠只穿线不接扎;造模24 h后,黄芪甲甙组大鼠腹腔注射黄芪甲甙20 mg·kg-1·d-1,假手术组、模型组大鼠腹腔注射相同体积的羧甲基纤维素钠,每日1次,连续2周。分别于造模前、造模后即刻及给药1、3、7、14 d描记肢体Ⅱ导联心电图,观察ST 段变化。给药2周后,检测各组大鼠左心室舒张末期内径(LVDD)、左心室收缩末期内径(LVDS)、左心室舒张末期容积(LVEDV)、左心室收缩末期容积(LVESV)、左心室短轴的缩短率(LVFS)及左心室射血分数(LVEF);应用酶联免疫吸附试验法检测各组大鼠血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)及核转录因子-κB(NF-κB)水平,并检测血浆一氧化氮(NO)水平;实时荧光定量聚合酶链反应检测各组大鼠心肌组织中Toll样受体(TLR)2、TLR4、核苷酸结合寡聚化结构域(NOD)1、NOD2及内皮型一氧化氮合酶(eNOS)mRNA的表达。结果 造模过程中,假手术组、模型组、黄芪甲甙组大鼠分别死亡0、4、2只。模型组和黄芪甲甙组大鼠造模后即刻及给药后1、3、7、14 d ST段值均显著高于假手术组(P<0.01)。黄芪甲甙组大鼠给药后3、7、14 d ST段值均显著低于模型组(P<0.05)。与假手术组比较,模型组和黄芪甲甙组大鼠LVDD、LVDS显著扩大(P<0.01),LVEDV、LVESV显著增加(P<0.01),LVFS、LVEF显著下降(P<0.01);血清IL-1β、IL-6、TNF-α水平和心肌组织中TLR2、TLR4、NOD1、NOD2 mRNA水平显著增加(P<0.01);血浆NO水平显著降低 (P<0.05)。模型组大鼠血清NF-κB水平高于假手术组(P<0.01),心肌组织中eNOS mRNA表达低于假手术组(P<0.05)。黄芪甲甙组与假手术组大鼠血清NF-κB水平和心肌组织中eNOS mRNA表达比较差异无统计学意义(P>0.05)。与模型组比较,黄芪甲甙组大鼠LVDD、LVDS显著缩小(P<0.05),LVEDV、LVESV显著下降(P<0.05),LVFS、LVEF显著增加(P<0.05);血清IL-1β、IL-6、TNF-α、NF-κB水平和心肌组织中TLR2、TLR4、NOD1、NOD2 mRNA表达显著降低(P<0.05);血浆NO水平和心肌组织中eNOS mRNA表达显著升高(P<0.05)。结论 黄芪甲甙对急性心肌梗死大鼠心脏具有保护作用,其机制可能与激活eNOS信号系统和抑制TLR信号途径有关。
Abstract:
Objective To evaluate the cardio protective effect of astragaloside in rats with acute myocardial infarction and investigate the potential molecular mechanisms.Methods Forty-five Wistar rats were randomly divided into sham operation group,model group and astragaloside group,with 15 rats in each group.The acute myocardial infarction model was prepared by permanently occluding the left anterior descending artery in the model group and the astragaloside group,while the rats in the sham operation group were threaded only.Twenty-four hours after operation,the rats in the astragaloside group received astragaloside 20 mg·kg-1·d-1 by intraperitoneal injection,once a day for two weeks.The rats in sham operation group and model group received isodose carboxymethylcellulose sodium by intraperitoneal injection,once a day for two weeks.Electrocardiogram was recorded to observe the changes of ST segment before ligation,after ligation immediately,1,3,7,14 d after intervened by astragaloside.Echocardiography was used to detect the left ventricular internal diameter at end-diastole (LVDD),left ventricular internal diameter at end-systole (LVDS),left ventricular end diastolic volume(LVEDV),left ventricular end systolic volume(LVESV),left ventricular fractional shortening(LVFS),left ventricular ejection fraction(LVEF).The levels of tumor necrosis factor alpha (TNF-α),interleukin(IL)-1β,IL-6,nuclear factor-κB(NF-κB) in serum were measured by enzyme linked immunosorbent assay and the level of nitric oxide(NO) in plasma was measured by reagent kid.The expressions of toll-like receptor(TLR)2,TLR4,nucleotide binding oligomerization do main(NOD)1,NOD2,endothelial nitric oxide synthase(eNOS) mRNA were detected by quantitative real-time polymerase chain reaction.Results During the operation,there was 0,4,2 dead rats in the sham operation group,model group and astragaloside group.The ST segment in the model group and astragaloside group was higher than that in the sham operation group after operation immediately,1,3,7,14 d after intervented by astragaloside(P<0.01).The ST segment in the astragaloside group was lower than that in the model operation group at the time of 1,3,7,14 d after intervented by astragaloside(P<0.05).Compared with the sham operation group,the LVDD,LVDS,LVEDV,LVESV increased (P<0.01),LVFS,LVEF decreased (P<0.01),the levels of TNF-α,IL-1β,IL-6 and the expression of TLR2,TLR4,NOD1,NOD2 mRNA in cardiac muscle tissue were higher in the model group and astragaloside group (P<0.01),the level of NO was lower (P<0.05).The level of serum NF-κB in the model group was higher than that in the sham operation group(P<0.01),the expression of the eNOS mRNA in cardiac muscle tissue was lower than that in the sham operation group(P<0.05).There was no significant difference in the level of serum NF-κB and the expression of the eNOS mRNA in cardiac muscle tissue between the astragaloside group and sham operation group (P>0.05).Compared with the model group,in the astragaloside group the LVDD,LVDS,LVEDV,LVESV decreased(P<0.05),but LVFS,LVEF increased (P<0.05),the levels of TNF-α,IL-1β,IL-6,NF-κB and the expression of TLR2,TLR4,NOD1,NOD2 mRNA in cardiac muscle tissue were lower(P<0.05),the level of NO and the expression of the eNOS mRNA in cardiac muscle tissue were higher(P<0.05).Conclusion Astragaloside has protective effect against to acute myocardial infarction induced injury by decreasing the expression of TLR signal path and activating eNOS signaling.

参考文献/References:

[1] 何忠开,姚峰,梁政,等.白藜芦醇对急性心肌梗死大鼠核因子-κB 信号通路表达的影响[J].新乡医学院学报,2017,34(4):251-254.
[2] AKASAKA Y,MORIMOTO N,ISHIKAWA Y,et al.Maocardial apoptosis associated with the expression of proinflammatory cytokines during the course of myocardial infarction[J].Mod Pathol, 2006,19(4):588-598.
[3] HAUDEK S B,TAFFET G E,SCHNEIDER M D,et al.TNF provokes cardiomyocyte apoptosis and cardiac remodeling through activation of multiple cell death pathways[J].J Clin Invest,2007,117 (9):2692-2701.
[4] KARPINSKI L,PNAKSEJ R,KOSMALA W,et al.Serum levels of interleukin-6,interleukin-10 and C-reactive protein in relation to left ventricular function in patients with myocardial infarction treated with primary angioplasty[J].Kardiol Pol,2008,66(12): 1279-1285.
[5] 路妍,张建华.瑞舒伐他汀对急性心肌梗死患者行择期PCI术后外周血TLR4表达及炎性因子的影响[J].河北医药,2015,37(23):3544-3547.
[6] HU Z P,FANG X L,FANG N,et al.Melatonin ameliorates vascular endothelial dysfunction,inflammation,and atheroscelrosis by suppressing the TLR4 /NF-κB system in high-fat-fed rabbits[J].J Pineal Res,2013,55(4):388-398.
[7] ISHIKAWA Y,SATOH M,ITOH T,et al.Local expression of Toll-like receptor 4 at the site of ruptured plaques in patients with acute myocardial infarction[J].Clin Sci,2008,115(4):133-140.
[8] 梁荣寿,李健哲.黄芪注射液对脂多糖诱导的内皮细胞炎症因子产生的影响及其机制研究[J].中国临床药理学与治疗学,2011,16(6):611-616.
[9] 李青,许陵冬,江燕,等.黄芪甲苷对肾小管上皮细胞诱导单核细胞分化的影响[J].临床肾脏病杂志,2016,9(16):557-561.
[10] 于俊民,张小波,姜文,等.黄芪总皂苷对大鼠缺血心肌血管内皮生长因子蛋白表达的影响[J].中国急救医学,2014,34(11):1033-1035.
[11] TANG Y L,ZHAO Q,QIN X,et al.Paraerine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction[J].Ann Thorac Surs,2005,80(1):229-236.
[12] 朱丹,郭艳红,米琳,等.大鼠心肌梗死模型心功能评价的方法学比较[J].中国微创外科杂志,2009,9(5):413-416.
[13] 孙园园,郭大东,陈美清,等.rno-miR-30b-5p在葡萄膜炎发病过程中对白细胞介素-10和Toll样受体4表达的调控作用[J].眼科新进展,2017,37(4):330-332.
[14] 刘晶,白浪,苏亚茹,等.不同浓度肽聚糖对角膜上皮细胞Toll样受体(TLR)2和TLR4表达的影响[J].眼科新进展,2017,37(8):705-708.
[15] ZHAO P,WANG J,HE L,et al.Deficiency in TLR4 signal transduction ameliorates cardiac injury and cardiomyocyte contractile dysfunction during ischemia[J].J Cell Mol Med,2009,13(8A):1513-1525.
[16] 马丽霞,袁青,刘佳佳.Nod样受体与Toll受体介导炎症的研究进展[J].国际免疫学杂志,2009,32(5):345-349.
[17] 陈琳琳,卢放根.固有免疫中TLR和NOD的研究现状[J].国际免疫学杂志,2008,31(6):461-465.
[18] 武宇辉,齐颖,马伟科,等.微小RNA-155和微小RNA-21对脓毒症患儿Toll样受体4表达的影响[J].中华实用儿科临床杂志,2017,32(6):420-424.
[19] 张静,禚志红,王怀立,等.脂多糖预处理对癫痫幼鼠Toll样受体4/高迁移率族蛋白1基因表达及海马硬化的影响[J].中华实用儿科临床杂志,2016,31(21):1658-1662.
[20] 宋亚辉,尤庆旺,王倩楠,等.Omega-3鱼油脂肪乳对缺氧缺血性脑损伤新生大鼠海马组织Toll样受体4和核因子κB的影响[J].中华实用儿科临床杂志,2016,31(12):923-926.
[21] 韩梦雨,金明,王志军.炎性细胞因子与新生血管性眼病[J].眼科新进展,2017,37(12):1088-1092.
[22] MOON M K,LEE Y J,KIM J S,et al.Effect of caffeic acid on tumor necrosis factor-alpha -induced vascular inflammation in human umbilical vein endothelial cells[J].Biol Pham Bull,2009,32(8):1371-1377.
[23] TESTA M,YEH M,LEE P,et al.Circulating levels of cytokines and their endogenous modulators in patients with mild to severe congestive heart failure due to coronary artery disease or hypertension[J].J Am Coll Cardiol,1996,28(4):964-971.
[24] TURNER N A,DAS A,WARBURTON P,et al.Interleukin-lalpha stimulates proinflammatory cytokine expression in human cardiac myofibroblasts[J].Am J Physiol Heart Circ Physiol,2009,297(3): H1117-H1127.
[25] BALLIGAND J L,CANNON P J.Nitric oxide synthases and cardiac muscle.Autocrine and paracrine influences[J].Arterioscler Thromb Vasc Biol,1997,17(10): 1846-1858.
[26] SUMERAY M S,REES D D,YELLON D M.Infarct size and nitric oxide synthase in murine myocardium[J].J Mol Cell Cardiol,2000,32(1): 35-42.

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更新日期/Last Update: 2018-03-05