Prediction and validation of the mechanism of Zadi-5 pill in protecting myocardial ischemia-reperfusion injury

Wuriga; Weilisi; Wurilaga; Susi; Aruhan; TONG Lijun; Butuya; Hurilebagen

doi:10.6039/j.issn.1001-0408.2024.04.11

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Prediction and validation of the mechanism of Zadi-5 pill in protecting myocardial ischemia-reperfusion injury

更新时间：2024-02-23

- Prediction and validation of the mechanism of Zadi-5 pill in protecting myocardial ischemia-reperfusion injury
- ZHONGGUO YAOFANG Vol. 35, Issue 4, Pages: 442-448(2024)
- 作者机构：
  
  内蒙古医科大学蒙医药学院，呼和浩特　010110
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.04.11
  CLC： R965;R29
- Published：29 February 2024，
  
  Received：13 August 2023，
  
  Revised：26 January 2024，
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,威力 ,,苏 ,,阿茹等.匝迪-5味丸改善心肌缺血再灌注损伤的作用机制预测及验证 ^Δ[J].中国药房,2024,35(04):442-448.

Wuriga ,Weilisi ,Wurilaga ,et al.Prediction and validation of the mechanism of Zadi-5 pill in protecting myocardial ischemia-reperfusion injury[J].ZHONGGUO YAOFANG,2024,35(04):442-448.
,威力 ,,苏 ,,阿茹等.匝迪-5味丸改善心肌缺血再灌注损伤的作用机制预测及验证 ^Δ[J].中国药房,2024,35(04):442-448. DOI： 10.6039/j.issn.1001-0408.2024.04.11.

Wuriga ,Weilisi ,Wurilaga ,et al.Prediction and validation of the mechanism of Zadi-5 pill in protecting myocardial ischemia-reperfusion injury[J].ZHONGGUO YAOFANG,2024,35(04):442-448. DOI： 10.6039/j.issn.1001-0408.2024.04.11.

摘要

目的

探讨匝迪-5味丸改善心肌缺血再灌注损伤（MIRI）的作用机制。

方法

通过网络药理学方法筛选匝迪-5味丸改善MIRI的潜在作用靶点和通路。将72只大鼠随机分为模型组、假手术组、丹参组[复方丹参滴丸80 mg/（kg·d）]和匝迪-5味丸高、中、低剂量组[1.6、0.8、0.4 g/（kg·d）]，每组12只。各组大鼠灌胃相应药物，每天1次，连续14 d。末次给药后，结扎大鼠左冠状动脉前降支建立MIRI模型，假手术组大鼠只穿线不结扎。检测建模后各组大鼠血清中肌酸激酶（CK）、乳酸脱氢酶（LDH）、天冬氨酸转氨酶（AST）、心肌肌钙蛋白T（CTn-T）的含量，心肌细胞凋亡率，心肌组织中磷脂酰肌醇3-激酶（PI3K）、蛋白激酶B（Akt）、B淋巴细胞瘤2（Bcl-2）及Bcl-2相关X蛋白（Bax）、胱天蛋白酶3（caspase-3）蛋白表达水平；观察心肌组织形态变化。

结果

共获得匝迪-5味丸的活性成分177个，作用靶点220个，参与改善心肌缺血相关的靶点51个，其中核心靶点为

AKT1

，涉及PI3K-Akt、内质网、缺氧诱导因子-1等多个通路。与模型组比较，丹参组和匝迪-5味丸高剂量组大鼠血清中CK、LDH、AST、CTn-T含量和心肌细胞凋亡率，以及心肌组织中caspase-3、Bax蛋白表达水平均显著降低（

＜0.05或

＜0.01），心肌组织中PI3K、Akt、Bcl-2蛋白表达水平均显著升高（

＜0.05或

＜0.01），心肌组织病理形态改变均明显改善；匝迪-5味丸低、中剂量组大鼠上述指标亦有不同程度改善。

结论

匝迪-5味丸可能通过激活PI3K-Akt信号通路抑制细胞凋亡，从而发挥改善MIRI的作用。

Abstract

OBJECTIVE

To explore the mechanism of Zadi-5 pill in improving myocardial ischemia-reperfusion injury （MIRI）.

METHODS

The targets and pathways of potential effects of Zadi-5 pill improving MIRI were screened based on the network pharmacology. Seventy-two rats were randomly divided into model group， sham operation group， Danshen group [Compound danshen dripping pills 80 mg/（kg·d）] and Zadi-5 pill high-dose， medium-dose and low-dose groups [1.6， 0.8， 0.4 g/（kg·d）]， with 12 rats in each group. The rats in each group were given corresponding drugs intragastrically， once a day， for 14 consecutive days. After the last administration， MIRI model was established by ligating the anterior descending branch of left coronary artery in rats， while rats in the sham operation group were threaded without ligation. The contents of creatine kinase （CK）， lactate dehydrogenase （LDH）， aspartate transaminase （AST）， cardiac troponin T （CTn-T）， apoptotic rate of cardiomyocyte， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 related X protein （Bax） and caspase-3 in myocardial tissue were detected in each group after modeling； the morphological changes of myocardial tissue were observed.

RESULTS

A total of 177 active ingredients and 220 targets of Zadi-5 pill were obtained， including 51 targets involved in improving myocardial ischemia； the core target of Zadi-5 pill improving MIRI was

AKT1

， including PI3K-Akt， endoplasmic reticulum and hypoxia-inducible factor-1. Compared with model group， the contents of CK， LDH， AST and CTn-T， the apoptotic rate of cardiomyocyte as well as the protein expressions of caspase-3 and Bax were significantly decreased in Danshen group and Zadi-5 pill high-dose group （

＜0.05 or

＜0.01）， while the protein expressions of PI3K， Akt and Bcl-2 in myocardial tissue were significantly increased （

＜0.05 or

＜0.01）， respectively； the myocardial histopathological changes were significantly improved. The above indicators were improved to varying degrees in Zadi-5 pill low-dose and medium-dose groups， too.

CONCLUSIONS

Zadi-5 pill may inhibit apoptosis by activating the PI3K-Akt signaling pathway， thus playing a role in improving MIRI.

关键词

匝迪-5味丸心肌缺血再灌注损伤作用机制磷脂酰肌醇3-激酶/蛋白激酶B信号通路凋亡

Keywords

myocardial ischemic-reperfusion injurymechanism of actionphosphatidylinositol 3-kinase/Akt signaling pathwayapoptosis

references

中国心血管健康与疾病报告编写组. 中国心血管健康与疾病报告2021概要[J]. 中国循环杂志，2022，37（6）：553-578.

The Writing Committee of the Report on Cardiovascular Health and Diseases in China. Report on cardiovascular health and diseases in China 2021：an updated summary[J]. Chin Circ J，2022，37（6）：553-578.

吉格木德丹僧扎木苏.通瓦嘎吉德[M].呼和浩特：内蒙古人民出版社，1999：65．

Jigmudanzenjamsu. Tongwagajid[M]. Hohhot：Inner Mongolia People’s Publishing House，1999：65.

苏德. 蒙药治疗冠心病心绞痛的疗效观察[J/OL]. 中西医结合心血管病电子杂志，2016，4（10）：13-14[2023-07-13]. https：//kns.cnki.net/KCMS/detail/detail.aspx?dbcode=CJFD&filename=ZXJH201610007https://kns.cnki.net/KCMS/detail/detail.aspx?dbcode=CJFD&filename=ZXJH201610007.

SU D. Observation on therapeutic effect of Mongolian medicine on angina pectoris of coronary heart disease[J/OL]. Cardiovasc Dis J Integr Tradit Chin West Med，2016，4（10）：13-14[2023-07-13]. https：//kns.cnki.net/KCMS/detail/detail.aspx?dbcode=CJFD&filename=ZXJH-201610007https://kns.cnki.net/KCMS/detail/detail.aspx?dbcode=CJFD&filename=ZXJH-201610007.

段·贡布扎布.高氏梅林方[M].赤峰：内蒙古科学技术出版社，1999：6，106.

DUAN G. Gaoshimeilin prescription[M]. Chifeng：Inner Mongolia Science and Technology Press，1999：6，106.

威力斯，苏斯，苏尼尔，等. 匝迪-5味丸对心肌缺血再灌注损伤模型大鼠的心肌保护作用研究[J]. 中国民族医药杂志，2021，27（12）：50-53.

Weilisi，Susi，Sunier，et al. Protective effect of Zadi-5 pill on myocardial ischemia-reperfusion injury model rats[J]. J Med Pharm Chin Minor，2021，27（12）：50-53.

额尼日乐.蒙药匝迪-5对缺血再灌注损伤模型大鼠的心肌保护作用机制研究[D].北京：北京中医药大学，2021.

Enirile. Mechanism of myocardial protection of Mongolian medicine Zadi-5 in myocardial ischemia-reperfusion injury model rats[D]. Beijing：Beijing University of Traditional Chinese Medicine，2021.

翁锦龙，熊尚全，江澍，等. 瓜蒌薤白半夏汤预处理对心肌缺血再灌注损伤模型大鼠的心肌保护作用及机制研究[J]. 实用心脑肺血管病杂志，2023，31（12）：43-48，53.

WENG J L，XIONG S Q，JIANG S，et al. Protective effect and mechanism of pretreatment of Gualou xiebai banxia decoction on myocardial ischemia-reperfusion injury model rats[J]. Pract J Card Cereb Pneumal Vasc Dis，2023，31（12）：43-48，53.

CHEN X Y，ZHABYEYEV P，AZAD A K，et al. Endothelial and cardiomyocyte PI3Kβ divergently regulate cardiac remodeling in response to ischemic injury[J]. Cardiovasc Res，2019，115（8）：1343-1356.

宋焰桃，胡安群. 非酶类生物标志物在心肌损伤中的应用进展[J]. 国际检验医学杂志，2023，44（8）：1007-1012，1024.

SONG Y T，HU A Q. Application progress on non-enzymatic biomarkers in myocardial injury[J]. Int J Lab Med，2023，44（8）：1007-1012，1024.

赵博，屈新亮，王祁，等. 网络药理学预测四逆汤抗心肌缺血再灌注损伤机制及实验验证[J]. 中国实验方剂学杂志，2022，28（9）：168-175.

ZHAO B，QU X L，WANG Q，et al. Mechanism of Sinitang against myocardial ischemia-reperfusion injury：prediction based on network pharmacology and verification by cellular experiments[J]. Chin J Exp Tradit Med Formulae，2022，28（9）：168-175.

谢延峥，马金，邹旭. PI3K/Akt信号通路串扰在心肌缺血再灌注损伤中的作用及中医药防治进展[J]. 中国实验方剂学杂志，2020，26（24）：201-210.

XIE Y Z，MA J，ZOU X. Effect of PI3K/Akt signal pathway crosstalk in myocardial ischemia reperfusion injury and prevention and treatment with traditional Chinese medicine therapy[J]. Chin J Exp Tradit Med Formulae，2020，26（24）：201-210.

YI C L，SONG M J，SUN L F，et al. Asiatic acid alleviates myocardial ischemia-reperfusion injury by inhibiting the ROS-mediated mitochondria-dependent apoptosis pathway[J]. Oxid Med Cell Longev，2022，2022：3267450.

ZHANG Y，ZHANG J Q，ZHANG T，et al. Calycosin induces gastric cancer cell apoptosis via the ROS-mediated MAPK/STAT3/NF-κB pathway[J]. Onco Targets Ther，2021，14：2505-2517.

程安然，王钰滢，华健，等. 黄芪-葛根药对治疗糖尿病心肌病的理论探讨[J]. 中草药，2023，54（23）：7853-7861.

CHENG A R，WANG Y Y，HUA J，et al. Theoretical discussion on treatment of diabetic cardiomyopathy by Astra-gali Radix-Puerariae Lobatae Radix herb pair[J]. Chin Tradit Herbal Drugs，2023，54（23）：7853-7861.

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