丹参酮ⅡA对血瘀型大鼠急性心梗后心功能的影响

2020-08-21 08:52:38 中国现代医生 2020年18期

林冬铭 陈超 陆明 陈菲 王审 周亚萍 黄抒伟

[摘要] 目的 探討丹参酮ⅡA对急性心梗大鼠再灌注损伤的保护作用。 方法 选取30只SD大鼠,建立血瘀模型,随机分为假手术组(Sham组)、AMI对照组(Control组)及丹参酮ⅡA干预组(TSN组)。Sham组只开胸穿线不结扎,Control组与TSN组建立心梗再灌注模型。造模前、再灌注4周后观察各组的超声心动图,再灌注4周后比较各组的血流动力学结果。 结果 超声心动图结果显示Control组的左室收缩末内径(LVIDs)和左室舒张末内径(LVIDd)较Sham组扩大(P<0.05),左室射血分数及左室短轴缩短率较假手术组降低(P<0.05);TSN组与Control组相比,LVIDs及LVIDd有改善(P<0.05),且LVEF%及FS%得到提高(P<0.05)。血流动力学结果显示,再灌注4周后,Control组与假手术组比较,可见HR加快、LVSP下降、LVEDP升高(P<0.05);与Control组比较,TSN组能升高LVSP,降低LVEDP,差异有统计学意义(P<0.05),但HR则无差异(P>0.05)。 结论 丹参酮ⅡA可改善血瘀型大鼠急性心梗后的心功能。

[关键词] 丹参酮ⅡA;急性心肌梗死;无复流;心功能;大鼠

[中图分类号] R285.5          [文献标识码] A          [文章编号] 1673-9701(2020)18-0032-05

Impacts of tanshinone ⅡA on cardiac function after acute myocardial infarction in blood stasis rats

LIN Dongming1   CHEN Chao1   LU Ming1   CHEN Fei2   WANG Shen1   ZHOU Yaping3   HUANG Shuwei1

1.Department of Cardiovascular Internal Medicine, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, China; 2.Yunhe County Hospital of Traditional Chinese Medicine in Zhejiang Province, Yunhe   323600, China; 3.Zhejiang Chinese Medical University, Hangzhou   310053, China

[Abstract] Objective To investigate the salvage efficacy of tanshinone ⅡA on reperfusion injury in rats with acute myocardial infarction. Methods Thirty SD rats were randomly divided into sham operation group (the sham group), AMI control group (the control group) and tanshinone ⅡA intervention group (the TSN group) to establish blood stasis model. In the sham group,  only thoracotomy was performed without ligation. In the control group and the TSN group,  myocardial infarction reperfusion model was established. Echocardiography of each group was observed before modeling and four weeks after reperfusion, and hemodynamic results of each group were compared four weeks after reperfusion. Results Echocardiographic results showed that the left ventricular internal dimension in systole(LVIDs) and left ventricular internal dimension-diastole (LVIDd) in the control group were larger than those in the sham group(P<0.05),  and the left ventricular ejection fraction and left ventricular short-axis shortening rate were lower than those in the sham group(P<0.05). Compared with the control group, LVIDs and LVIDd in the TSN group were improved(P<0.05), and LVEF% and FS% were improved(P<0.05). Hemodynamic results showed that HR increased,  LVSP decreased and LVEDP increased in the control group compared with the sham operation group after four weeks of reperfusion(P<0.05). Compared with the control group,  the TSN group increased LVSP and decreased LVEDP with statistically significant differences(P<0.05),  but HR had no statistically significant difference(P>0.05). Conclusion Tanshinone ⅡA improves cardiac function after acute myocardial infarction in blood stasis rats.

注:假手术组(Sham组),模型组(Control组),丹参酮ⅡA干预组(TSN组)。Control组与Sham组比较,*P<0.05;TSN组与Control比较,#P<0.05

2.3 三组血流动力学检测

再灌注4周后,AMI对照组(Control组)与假手术组(Sham组)比较,可见心率(HR)加快、左室收缩压(LVSP)下降、左室舒张末压(LVEDP)升高,差异有统计学意义(P<0.05)。与AMI对照组(Control组)比较,丹参酮ⅡA干预组(TSN组)能升高LVSP,降低LVEDP,具有统计学意义(P<0.05),但HR则无差异(P>0.05)。见表3。

注:TSN组与Sham组比较,*P<0.05;TSN组与Control组比较,#P<0.05;TSN组与Control组比较,**P>0.05

2.4 Control组与TSN组心肌无复流面积和心肌梗死面积比较

再灌注4周后,Control组与TSN组相比缺血面积比相似(P>0.05),表明各组间基线一致,其梗死面积及无复流面积存在可比性。与Control组相比,TSN组的梗死面积和无复流面积缩小,有统计学差异(P<0.05)。见表4。

3 讨论

随着血运重建技术的发展,急性心肌梗死的死亡率得到了下降,但缺血再灌注损伤然仍是临床的重要课题[9]。现代研究显示缺血再灌注损伤主要机制与氧化应激、钙超载、炎症因子及线粒体膜通透性等存在相关性[10-13],但临床如何有效改善缺血再灌注损伤仍待深入探索,尤其是如何维护缺血损伤后的心功能更是临床重点。

我国传统中药具有多靶点、多作用机制的特点,在改善缺血再灌注损伤中发挥着重要的作用。祖国医药不仅能改善心肌缺血症状,还通过各种机制发挥抗缺血再灌注作用。研究显示,中医药可通过氧化应激相关机制改善心肌缺血再灌注损伤[14];同时也证明中医药可提升SOD的活力,降低MDA的含量,减轻心肌细胞损伤[15];亦有研究显示可改善心肌细胞中的炎症因子,并通过增加蛋白水平发挥抗损伤作用[16];并有研究认为中医药可改善大鼠心肌梗死,且机制与C反应蛋白与髓过氧化物酶相关[17]。

在改善急性心梗后心功能方面,祖国医学认为心力衰竭的发生其病机与血瘀密不可分,故往往采用活血化瘀为治法改善心功能。

丹参作为活血化瘀的代表药物,味苦,性微寒,归心、肝经,具有活血通络、祛瘀止痛、凉血消痈、清除心烦等功效。李时珍的《本草纲目》记载“丹参活血,通心包络”。丹参的药物主要有效成分分为水溶性成分(以丹参素和丹酚酸为代表)和脂溶性成分(以丹参酮为代表)。丹参酮ⅡA是丹参酮最具活性的化学结构,其具有更优的活血化瘀作用,还具有改善微循环、扩张冠状动脉、抑制血栓素生成、减少血小板黏附和聚集等作用,被广泛应用于心脑血管等领域。有研究表明,丹参酮ⅡA具有抗动脉粥样硬化作用,能减少心肌缺血和心肌缺血再灌注损伤[18-19];丹参酮ⅡA通过抑制ERK1/2MAPK信號抑制AGEs诱导的血管平滑肌细胞增殖和迁移[20]。

本研究组以丹参酮ⅡA为研究对象,项目组既往研究已证实其能缩小梗死面积,改善再灌注损伤[7-8]。本研究进一步探讨丹参酮ⅡA对心梗后心功能的保护作用。研究结果提示:大鼠心梗再灌注4周后,心超显示丹参酮ⅡA干预组能有效降低LVIDs及LVIDd,并提高LVEF%及FS%,同时,血流动力学结果亦显示,丹参酮ⅡA升高LVSP,降低LVEDP。两者均提示丹参酮ⅡA对心梗后的心功能有保护作用,对比心肌无复流面积和心肌梗死面积,提示丹参酮ⅡA能改善心功能,且改善心肌缺血和再灌注损伤与心功能的影响呈正相关。

本研究存在一定的局限性:(1)本研究样本量较小,丹参酮ⅡA对心功能的作用有待更多的研究进一步证实。(2)研究未涉及丹参酮ⅡA的作用机制,研究组下阶段拟扩大样本量,进行深化机制研究。

[参考文献]

[1] Mozaffarian D,Benjamin EJ,Go AS,et al.Executive summary:Heart disease and stroke statistics-2015 update:A report from the American Heart Association[J]. Circulation,2015,131(4):434-441.

[2] Li J,Li X,Wang Q,et al. ST-segment elevation myocardial infarction in China from 2001 to 2011(the China PEACE-Retrospective Acute Myocardial.Infarction Study):a retrospective analysis of hospital data[J]. Lancet,2015, 385(9966):441-451.

[3] Li J,Dharmarajan K,Li X,et al.China PEACE Collaborative Group.Protocol for the China PEACE(patient-centered evaluative assessment of cardiac events) retrospective study of coronary catheterisation and percutaneous coronary intervention[J].BMJ Open,2014,4(3):e004595.

[4] Kobusiak·Prokopowicz M,Krzysztofik J,Kaaz K,et a1.MMP-2 andTIMP-2 in patients with heart failare and chronic kidney disease[J].Open Med(Wars),2018,(13):237-246.

[5] Radosinska J,Barancik M,Vrbjar N.Heart failure and role of circulating MMP-2 and MMP-9[J].Panminerva Med,2017,59(3):241-253.

[6] 林冬铭,黄抒伟,陆明,等.丹参酮ⅡA对兔急性心梗再灌注后无复流的干预[J].中华中医药学刊,2013.31(7):1649-1651.

[7] 王琳莉,黄抒伟,窦丽萍,等.丹参酮IIA磺酸钠对兔急性心梗再灌注后无复流的保护作用[J].中华中医药学刊,2016,34(3):678-682.

[8] 苗兰,潘映红,任建勋,等.气滞血瘀证模型大鼠血清蛋白质组学初步研究[J].中国中医基础医学杂志,2008, 14(2):106-107.

[9] 陈伟伟,高润霖,刘力生,等.《中国心血管病报告2014》概要[J].中国循环杂志,2015,(7):617-622.

[10] CuggTT,Morel 0,Cayla G,et al.Cyclosporine before PCI in patients with acute myocardial infarction[J].N Engl J Med,2015,373(11):1021-1031.

[11] Kalogeris T,Baines CP,Krenz M,et al.Ischemia/reperfusion[J].Compr Physiol,2016,7:113-170.

[12] Kohlhauer M,Pell VR,Burger N,et al.Protection against cardiac ischemia-reperfusion injury by hypothermia and by inhibition of succinale accumulation and oxidation is additive[J].Basic Res Cardiol,2019,114:18.

[13] Hu H,Zhai C,Qian G,et al. Protective effects of tanshinone ⅡA on myocardial ischemia reperfusion injury by reducing oxidative stress,HMGB1 expression,and inflammatory reaction[J]. Pharm Biol,2015,53(12):1752-1758.

[14] Liu H,Wang C,Qiao Z,et al.Protective effect of curcumin against myocardium injury in ischemia reperfusion rats[J].Pharm Biol,2017,55:1144-1148.

[15] 蔡智慧,尹麗,常全忠.栀子苷预处理对H9C2心肌细胞缺氧/复氧损伤的影响及机制研究[J].天津中医药,2016,33(2):111-113.

[16] 张会超,徐里,芮浩淼等.苦豆碱对缺血再灌注引起的H9C2心肌细胞损伤和炎症应答的作用[J].中国病理生理杂志,2018,34(2):281-286.

[17] Refli Hasan,Dharma Lindarto.The effect of bay leaf extract Syzygium polyanthum (Wight) Walp. on C-reactive protein (CRP) and myeloperoxidase (MPO) level in the heart of rat model of myocardial infarction[J].Med Glas (Zenica),2020,17(1):78-82.

[18] Hu Q,Wei B,Wei L,et al.Sodium tanshinone ⅡA sulfonate ameliorates ischemia-induced myocardial inflammation and lipid accumulation in Beagle dogs through NLRP3 inflammasome[J].Int J Cardiol,2015,196:183-192.

[19] Chen Z,Xu H. Anti-inflammatory and immunomodulatory mechanism of tanshinone ⅡA for atherosclerosis[J].Evid Based Complement Alternat Med,2014,2014:267976.

[20] Ming Lu,Ying Luo,Pengfei Hu,et al. Tanshinone IIA inhibits AGEs-induced proliferation and migration of cultured vascular smooth muscle cells by suppressing ERK1/2 MAPK signaling[J].Iranian Journal of Basic Medical Sciences,2017,21:83-88.

(收稿日期:2020-04-10)