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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

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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, P<0.01 for all). In contrast, the rats in the low- and high-dose STDP pretreatment groups showed a significant decrease in coronary microthrombi (P<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 (P<0.05 or P<0.01).

Conclusion

STDP may be useful for treatment of CME, possibly via regulation of mPTP opening and AKT/GSK3β phosphorylation.

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References

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

    Article  Google Scholar 

  2. Lin ACW, Seale H, Hamilton-Craig C, Morris NR, Strugnell W. 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.

    Article  Google Scholar 

  3. Wang H, Zhong WJ, Huang MW, Wu XY, Chen H. 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.

    Article  CAS  Google Scholar 

  4. Zhang XY, Sun Y, Yang XY, Hu JY, Zheng R, Chen SQ, 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 2019 May 15. [Epub ahead of print]

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

    PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. Zhang H, Xu D, Yan L, Yuan L, Jia J, Sun A, 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.

    Google Scholar 

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

    Article  Google Scholar 

  10. Zhu H, Ding Y, Xu X, Li M, Fang Y, Gao B, 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.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. Li WZ, Yang Y, Liu K, Long R, Jin N, Huang SY, 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.

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  14. Shao L, Wu D, Zhang P, Li W, Wang J, Su G, 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.

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  16. Rolo AP, Teodoro JS, Peralta C, Rosello-Catafau J, Palmeira CM. 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.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  24. Zhang XH, Li M, Kang YJ, Xie YQ, Cao YX. 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.

    PubMed  Google Scholar 

  25. Nikolaou PE, Boengler K, Efentakis P, Vouvogiannopoulou K, Zoga A, Gaboriaud-Kolar N, 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.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  27. Fang R, Zhang LL, Zhang LZ, Li W, Li M, Wen K. 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.

    Article  CAS  Google Scholar 

  28. Si H, Zhang Y, Song Y, Li L. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Central Laboratory, Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China

    Yu Ding

  2. Department of Cardiology, Hangzhou Chinese Medical Hospital, Hangzhou, 310007, China

    Hou-yong Zhu

  3. Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou, 310053, China

    Li-zong Zhang

  4. Department of Cardiology, Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China

    Bei-bei Gao, Liang Zhou & Jin-yu Huang

Authors
  1. Yu Ding
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  2. Hou-yong Zhu
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  3. Li-zong Zhang
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  4. Bei-bei Gao
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  5. Liang Zhou
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  6. Jin-yu Huang
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Corresponding author

Correspondence to Jin-yu Huang.

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Conflict of Interest

The authors declare no financial or commercial conflict of interest.

Author Contributions

Ding Y and Huang JY designed the study and the project proposal. Ding Y and Zhu HY performed the molecular experiments, Zhang LZ performed the animal experiments, Gao BB and Zhou L analyzed the data. Ding Y and Huang JY wrote the paper.

Supported by the Zhejiang Provincial Administration of Traditional Chinese Medicine (No. 2018ZB082), Beijing Lisheng Cardiovascular Health Foundation of China (No. LSG1501132) and Zhejiang Natural Science Foundation (No. Y15H020003)

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Ding, Y., Zhu, Hy., Zhang, Lz. 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. Chin. J. Integr. Med. 27, 527–533 (2021). https://doi.org/10.1007/s11655-019-3176-6

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  • DOI: https://doi.org/10.1007/s11655-019-3176-6

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