Shexiang Tongxin Dropping Pill (麝香通心滴丸) Reduces Coronary Microembolization in Rats via Regulation of Mitochondrial Permeability Transition Pore Opening and AKT-GSK3β Phosphorylation

Yu DING; Hou-yong ZHU; Li-zong ZHANG; Bei-bei GAO; Liang ZHOU; Jin-yu HUANG

doi:10.1007/s11655-019-3176-6

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Shexiang Tongxin Dropping Pill (麝香通心滴丸) Reduces Coronary Microembolization in Rats via Regulation of Mitochondrial Permeability Transition Pore Opening and AKT-GSK3β Phosphorylation

Original Article | Updated：2021-09-01

- Shexiang Tongxin Dropping Pill (麝香通心滴丸) Reduces Coronary Microembolization in Rats via Regulation of Mitochondrial Permeability Transition Pore Opening and AKT-GSK3β Phosphorylation
- Shexiang Tongxin Dropping Pill (麝香通心滴丸) Reduces Coronary Microembolization in Rats via Regulation of Mitochondrial Permeability Transition Pore Opening and AKT-GSK3β Phosphorylation
- Chinese Journal of Integrative Medicine 2021年27卷第7期页码：527-533
- Affiliations：
  
  1.Central Laboratory, Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou (310006), China
  2.Department of Cardiology, Hangzhou Chinese Medical Hospital, Hangzhou (310007), China
  3.Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou (310053), China
  4.Department of Cardiology, Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou (310006), China
- Author bio：
  
  Prof. HUANG Jin-yu, E-mail: hjyu41@sohu.com
- Funds：
  
  the Zhejiang Provincial Administration of Traditional Chinese Medicine(2018ZB082);Beijing Lisheng Cardiovascular Health Foundation of China(LSG1501132);Zhejiang Natural Science Foundation(Y15H020003)
- DOI：10.1007/s11655-019-3176-6
  中图分类号：
- 纸质出版日期：2021-07-01，
  
  网络出版日期：2020-01-04，
  
  录用日期：2019-03-20
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Yu DING, Hou-yong ZHU, Li-zong ZHANG, 等. Shexiang Tongxin Dropping Pill (麝香通心滴丸) Reduces Coronary Microembolization in Rats via Regulation of Mitochondrial Permeability Transition Pore Opening and AKT-GSK3β Phosphorylation[J]. Chinese Journal of Integrative Medicine, 2021,27(7):527-533.

Yu DING, Hou-yong ZHU, Li-zong ZHANG, et al. Shexiang Tongxin Dropping Pill (麝香通心滴丸) Reduces Coronary Microembolization in Rats via Regulation of Mitochondrial Permeability Transition Pore Opening and AKT-GSK3β Phosphorylation[J]. Chinese Journal of Integrative Medicine, 2021,27(7):527-533.
Yu DING, Hou-yong ZHU, Li-zong ZHANG, 等. Shexiang Tongxin Dropping Pill (麝香通心滴丸) Reduces Coronary Microembolization in Rats via Regulation of Mitochondrial Permeability Transition Pore Opening and AKT-GSK3β Phosphorylation[J]. Chinese Journal of Integrative Medicine, 2021,27(7):527-533. DOI： 10.1007/s11655-019-3176-6.

Yu DING, Hou-yong ZHU, Li-zong ZHANG, et al. Shexiang Tongxin Dropping Pill (麝香通心滴丸) Reduces Coronary Microembolization in Rats via Regulation of Mitochondrial Permeability Transition Pore Opening and AKT-GSK3β Phosphorylation[J]. Chinese Journal of Integrative Medicine, 2021,27(7):527-533. DOI： 10.1007/s11655-019-3176-6.

摘要

Abstract

Objective:

To investigate the protective effects of Shexiang Tongxin Dropping Pill (麝香通心滴丸

STDP) following sodium laurate-induced coronary microembolization (CME) in rats.

Methods:

Forty rats were divided into 4 groups: the control (sham) group

CME group

low-dose STDP pretreatment group (20 mg•kg

-1

•d

-1

)

and high-dose STDP pretreatment group (40 mg•kg

-1

•d

-1

). The rats were intragastric administrated with STDP 2 weeks before operation. Moreover

the histopathological alterations were observed using optical microscopy and transmission electron microscopy. Antioxidant biomarkers were analyzed by enzyme-linked immunosorbent assay. Mitochondrial functions including the mitochondrial permeability transition pore (mPTP) mtDNA copy number were determined and proteins of AKT/GSK3β were analyzed by Western blot.

Results:

The rats in the CME group showed a significant increase in the fibrinogen-like protein 2 expression level and mitochondrial dysfunction and a decrease in the expression level of antioxidant biomarkers (superoxide dismutase and catalase

0.01 for all). In contrast

the rats in the low- and high-dose STDP pretreatment groups showed a significant decrease in coronary microthrombi (

0.05); moreover

STDP restored the antioxidant-related protein activities and mitochondrial function

inhibited mPTP opening

decreased AKT-Ser473 phosphorylation

and increased GSK3β-Ser9 phosphorylation (

0.05 or

0.01).

Conclusion:

STDP may be useful for treatment of CME

possibly via regulation of mPTP opening and AKT/GSK3β phosphorylation.

关键词

Keywords

Shexiang Tongxin Dropping PillChinese medicinecoronary microembolizationmitochondrial permeability transition poreAKTGSK3β

references

G Heusch, A Skyschally, P Kleinbongard. Coronary microembolization and microvascular dysfunction. Int J Cardiol 2018;258:17-23.

ACW Lin, H Seale, C Hamilton-Craig, NR Morris, W Strugnell. Quantification of biventricular strain and assessment of ventriculo-ventricular interaction in pulmonary arterial hypertension using exercise cardiac magnetic resonance imaging and myocardial feature tracking. J Magn Reson Imaging 2019;49:1427-1436.

H Wang, WJ Zhong, MW Huang, XY Wu, H Chen. Efficacy of dual antiplatelet therapy combined with Naoxintong Capsules following coronary microembolization induced by homologous microthrombi in rats. Chin J Integr Med 2011;17:917-924.

XY Zhang, Y Sun, XY Yang, JY Hu, R Zheng, SQ Chen, et al. Effect of Chinese medicine on no or slow reflow after percutaneous coronary intervention in myocardial infarction patients: a systematic review and meta-analysis. Chin J Integr Med 2020;26:227-234.

Q Su, X Lyu, Z Ye. Ligustrazine attenuates myocardial injury induced by coronary microembolization in rats by activating the PI3K/Akt pathway. Oxid Med Cell Longev 2019;2019:6791457.

DC Wallace, W Fan. Energetics, epigenetics, mitochondrial genetics. Mitochondrion 2010;10:12-31.

O Gateau-Roesch, L Argaud, M Ovize. Mitochondrial permeability transition pore and postconditioning.Cardiovasc Res 2006;70:264-273.

H Zhang, D Xu, L Yan, L Yuan, J Jia, A Sun, et al. The protective function of Shexiang on endothelial injury induced by angiotensin Ⅱ osmotic pump in the rat. Chin J Clin Med 2009;16:669-672.

M Xiong, C Jia, J Cui, P Wang, X Du, Q Yang, et al.Shexiang Tongxin Dropping Pill attenuates atherosclerotic lesions in ApoE deficient mouse model. J Ethnopharmacol 2015;159:84-92.

H Zhu, Y Ding, X Xu, M Li, Y Fang, B Gao, et al.Prostaglandin E1 protects coronary microvascular function via the glycogen synthase kinase 3β-mitochondrial permeability transition pore pathway in rat hearts subjected to sodium laurate-induced coronary microembolization. Am J Transl Res 2017;9:2520-2534.

S Lin, J Chu, L Zhang, D Chen, F Xiao, H Chen, et al.Protective effects of Shexiang Tongxin Dropping Pill on pituitrin-induced acute myocardial ischemia in rats. Mol Med Rep 2017;16:3125-3132.

WZ Li, Y Yang, K Liu, R Long, N Jin, SY Huang, et al. FGL2 prothrombinase contributes to the early stage of coronary microvascular obstruction through a fibrin-dependent pathway. Int J Cardiol 2019;274:27-34.

A Ghanekar, M Mendicino, H Liu, W He, M Liu, R Zhong, et al. Endothelial induction of fgl2 contributes to thrombosis during acute vascular xenograft rejection. J Immunol 2004;172:5693-5701.

L Shao, D Wu, P Zhang, W Li, J Wang, G Su, et al. The significance of microthrombosis and fgl2 in no-reflow phenomenon of rats with acute myocardial ischemia/reperfusion. Clin Appl Thromb Hemost 2013;19:19-28.

Y Ding, BH Xia, CJ Zhang, GC Zhuo. Mitochondrial tRNALeu (UUR) C3275T, tRNAGln T4363C and tRNALys A8343G mutations may be associated with PCOS and metabolic syndrome. Gene 2018;642:299-306.

AP Rolo, JS Teodoro, C Peralta, J Rosello-Catafau, CM Palmeira. Prevention of I/R injury in fatty livers by ischemic preconditioning is associated with increased mitochondrial tolerance: the key role of ATP synthase and mitochondrial permeability transition. Transpl Int 2009;22:1081-1090.

Z Wang, J Ding, X Luo, S Zhang, G Yang, Q Zhu, et al.Effect of allopurinol on myocardial energy metabolism in chronic heart failure rats after myocardial infarct. Int Heart J 2016;57:753-759.

M Bayeva, M Gheorghiade, H Ardehali. Mitochondria as a therapeutic target in heart failure. J Am Coll Cardiol 2013;61:599-610.

J Hoeks, P Sdchrauwen. Muscle mitochondria and insulin resistance: a human perspective. Trends Endocrinol Metab 2012;23:444-450.

HC Lee, PH Yin, CY Lu, CW Chi, YH Wei. Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells. Biochem J 2000;348:425-432.

SB Ong, P Samangouei, SB Kalkhoran, DJ Hausenloy. The mitochondrial permeability transition pore and its role in myocardial ischemia reperfusion injury. J Mol Cell Cardiol 2015;78:23-34.

Y Qiu, T Yu, W Wang, K Pan, D Shi, H Sun. Curcumin-induced melanoma cell death is associated with mitochondrial permeability transition pore (mPTP) opening.Biochem Biophys Res Commun 2014;448:15-21.

SB Ong, AB Gustafsson. New roles for mitochondria in cell death in the reperfused myocardium. Cardiovasc Res 2012;94:190-196.

XH Zhang, M Li, YJ Kang, YQ Xie, YX Cao. Long non-coding RNA LINP1 functions as an oncogene in endometrial cancer progression by regulating the PI3K/AKT signaling pathway. Eur Rev Med Pharmacol Sci 2019;23:6830-6838..

PE Nikolaou, K Boengler, P Efentakis, K Vouvogiannopoulou, A Zoga, N Gaboriaud-Kolar, et al. Investigating and re-evaluating the role of glycogen synthase kinase 3 beta kinase as a molecular target for cardioprotection by using novel pharmacological inhibitors. Cardiovasc Res 2019;115:1228-1243.

H Yao, X Han, X Han. The cardioprotection of the insulin-mediated PI3K/Akt/mTOR signaling pathway. Am J Cardiovasc Drugs 2014;14:433-442.

R Fang, LL Zhang, LZ Zhang, W Li, M Li, K Wen.Sphingosine 1-phosphate postconditioning protects against myocardial ischemia/reperfusion injury in rats via mitochondrial signaling and Akt-Gsk3β phosphorylation.Arch Med Res 2017;48:147-155.

H Si, Y Zhang, Y Song, L Li. Overexpression of adrenomedullin protects mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis via the Akt/GSK3β and Bcl-2 signaling pathways. Int J Mol Med 2018;41:3342-3352.

JF Zhang, L Zhang, LL Shi, ZH Zhao, H Xu, F Liang, et al. Parthenolide attenuates cerebral ischemia/reperfusion injury via Akt/GSK-3β pathway in PC12 cells. Biomed Pharmacother 2017;89:1159-1165.

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