Advertisement

Chinese Journal of Integrative Medicine

, Volume 23, Issue 1, pp 40–47 | Cite as

Salvianolate reduces murine myocardial ischemia and reperfusion injury via ERK1/2 signaling pathways in vivo

  • Jian-yong Qi
  • Juan Yu
  • Dong-hui Huang
  • Li-heng Guo
  • Lei Wang
  • Xin Huang
  • Hai-ding Huang
  • Miao Zhou
  • Min-zhou ZhangEmail author
  • Jiashin Wu
Original Article

Abstract

Objective

To analyze the effects of salvianolate on myocardial infarction in a murine in vivo model of ischemia and reperfusion (I/R) injury.

Methods

Myocardial I/R injury model was constructed in mice by 30 min of coronary occlusion followed by 24 h of reperfusion and pretreated with salvianolate 30 min before I/R (SAL group). The SAL group was compared with SHAM (no I/R and no salvianolate), I/R (no salvianolate), and ischemia preconditioning (IPC) groups. Furthermore, an ERK1/2 inhibitor PD98059 (1 mg/kg), and a phosphatidylinositol-3-kinase (PI3-K) inhibitor, LY294002 (7.5 mg/kg), were administered intraperitoneal injection (i.p) for 30 min prior to salvianolate, followed by I/R surgery in LY and PD groups. By using a double staining method, the ratio of the infarct size (IS) to left ventricle (LV) and of risk region (RR) to LV were compared among the groups. Correlations between IS and RR were analyzed. Western-blot was used to detect the extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (AKT) phosphorylation changes.

Results

There were no significant differences between RR to LV ratio among the SHAM, I/R, IPC and SAL groups (P>0.05). The SAL and IPC groups had IS of 26.1%±1.4% and 22.3%±2.9% of RR, respectively, both of which were significantly smaller than the I/R group (38.5%±2.9% of RR, P<0.05, P<0.01, respectively). Moreover, the phosphorylation of ERK1/2 was increased in SAL group (P<0.05), while AKT had no significant change. LY294002 further reduced IS, whereas the protective role of salvianolate could be attenuated by PD98059, which increased the IS. Additionally, the IS was not linearly related to the RR (r=0.23, 0.45, 0.62, 0.17, and 0.52 in the SHAM, I/R, SAL, LY and PD groups, respectively).

Conclusion

Salvianolate could reduce myocardial I/R injury in mice in vivo, which involves an ERK1/2 pathway, but not a PI3-K signaling pathway.

Keywords

ischemia and reperfusion injury salvianolate extracellular signal-regulated kinase 1/2 protein kinase B Chinese medicine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Notes

Acknowledgments

The authors thank Prof. GU Wei-wang (Laboratory Animal Center and Institute of Comparative Medicine, Southern Medical University) for general technique support and animal supply.

References

  1. 1.
    Papp R, Gönczi M, Kovács M, Seprényi G, Végh A. Gap junctional uncoupling plays a trigger role in the antiarrhythmic effect of ischaemic preconditioning. Cardiovasc Res 2007;74:396–405.CrossRefPubMedGoogle Scholar
  2. 2.
    Nilsson L, Hallén J, Atar D, Jonasson L, Swahn E. Early measurements of plasma matrixmetalloproteinase-2 predict infarct size and ventricular dysfunction in ST-elevation myocardial infarction. Heart 2012;98:31–36.CrossRefPubMedGoogle Scholar
  3. 3.
    Ueda N, Zipes DP, Wu J. Coronary occlusion and reperfusion promote early afterdepolarizations and ventricular tachycardia in a canine tissue model of type 3 long QT syndrome. Am J Physiol-Heart Circ Physiol 2006;290:H607–H612.CrossRefPubMedGoogle Scholar
  4. 4.
    Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med 2007;357:1121–1135.CrossRefPubMedGoogle Scholar
  5. 5.
    Ragosta M, Camarano G, Kaul S, Powers ER, Sarembock IJ, Gimple LW. Microvascular integrity indicates myocellular viability in patients with recent myocardial infarction. New insights using myocardial contrast echocardiography. Circulation 1994;89:2562–2569.PubMedGoogle Scholar
  6. 6.
    Ito H, Maruyama A, Iwakura K, Takiuchi S, Masuyama T, Hori M, et al. Clinical implications of the ‘no reflow’ phenomenon. A predictor of complications and left ventricular remodeling in reperfused anterior wall myocardial infarction. Circulation 1996;93:223–228.PubMedGoogle Scholar
  7. 7.
    Turer AT, Hill JA. Pathogenesis of myocardial ischemia/ reperfusion injury and rationale for therapy. Am J Cardiol 2010;106:360–368.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Liu J, Shen HM, Ong CN. Salvia miltiorrhiza inhibits cell growth and induces apoptosis in human hepatoma HepG(2) cells. Cancer Lett 2000;153:85–93.CrossRefPubMedGoogle Scholar
  9. 9.
    Wan JM, Sit WH, Lee CL, Fu KH, Chan DK. Protection of lethal toxicity of endotoxin by Salvia miltiorrhiza Bunge is via reduction in tumor necrosis factor alpha release and liver injury. Int Immunopharmacol 2006;6:750–758.CrossRefPubMedGoogle Scholar
  10. 10.
    Li X, Yu C, Sun W, Liu G, Jia J, Wang Y. Simultaneous determination of magnesium lithospermate B, rosmarinic acid, and lithospermic acid in beagle dog serum by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 2004;18:2878–2882.CrossRefPubMedGoogle Scholar
  11. 11.
    Zhang H, Zhang Y, Yang R, Li YJ, Wang M, Miao CL. Correlation study on effects of salvianolate on inflammatory cytokines of patients with acute coronary syndrome. Chin J Integr Tradit West Med (Chin) 2013;33:598–601.Google Scholar
  12. 12.
    Cheng TO. Cardiovascular effects of danshen. Int J Cardiol 2007;121:9–22.CrossRefPubMedGoogle Scholar
  13. 13.
    Wang F, Liu YY, Liu LY, Zeng QJ, Wang CS, Sun K, et al. The attenuation effect of 3, 4-dihydroxy-phenyl lactic acid and salvianolic acid B on venular thrombosis induced in rat mesentery by photochemical reaction. Clin Hemorheol Microcirc 2009;42:7–18.PubMedGoogle Scholar
  14. 14.
    Han JY, Horie Y, Fan JY, Sun K, Guo J, Miura S, et al. Potential of 3, 4-dihydroxy-phenyl lactic acid for ameliorating ischemia-reperfusion-induced microvascular disturbance in rat mesentery. Am J Physiol Gastrointest Liver Physiol 2009;296:G36–G44.CrossRefPubMedGoogle Scholar
  15. 15.
    Chan K, Chui SH, Wong DY, Ha WY, Chan CL, Wong RN. Protective effects of Danshensu from the aqueous extract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunction. Life Sci 2004;75:3157–3171.CrossRefPubMedGoogle Scholar
  16. 16.
    Yang GD, Zhang H, Lin R, Wang WR, Shi XL, Liu Y, et al. Down-regulation of CD40 gene expression and inhibition of apoptosis with Danshensu in endothelial cells. Basic Clin Pharmacol Toxicol 2009;104:87–92.CrossRefPubMedGoogle Scholar
  17. 17.
    Qi J, Yu J, Wang L, Guo L, Ma S, Huang D, et al. Tongguan Capsule protects against myocardial ischemia and reperfusion injury in mice. Evid Based Complement Alternat Med 2013;2013:159237.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Guo Y, Wu WJ, Qiu Y, Tang XL, Yang Z, Bolli R. Demonstration of an early and a late phase of ischemic preconditioning in mice. Am J Physiol 1998; 275:H1375–H387.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Ping P, Song C, Zhang J, Guo Y, Cao X, Li RC, et al. Formation of protein kinase C epsilon-Lck signaling modules confers cardioprotection. J Clin Invest 2002;109:499–507.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Xuan YT, Guo Y, Zhu Y, Wang OL, Rokosh G, Bolli R. Endothelial nitric oxide synthase plays an obligatory role in the late phase of ischemic preconditioning by activating the protein kinase C epsilon p44/42 mitogen activated protein kinase pSer-signal transducers and activators of transcription1/3 pathway. Circulation 2007;116:535–544.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Han B, Zhang X, Zhang Q, Zhao G, Wei J, Ma S, et al. Protective effects of salvianolate on microvascular flow in a porcine model of myocardial ischaemia and reperfusion. Arch Cardiovasc Dis 2011;104:313–324.CrossRefPubMedGoogle Scholar
  22. 22.
    Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature 2001;410:37–40.CrossRefPubMedGoogle Scholar
  23. 23.
    Ma XL, Kumar S, Gao F, Louden CS, Lopez BL, Christopher TA, et al. Inhibition of p38 mitogen-activated protein kinase decreases cardiomyocyte apoptosis and improves cardiac function after myocardial ischemia and reperfusion. Circulation 1999;99:1685–1691.CrossRefPubMedGoogle Scholar
  24. 24.
    Cheng TO. Danshen: a versatile Chinese herbal drug for the treatment of coronary heart disease. Int J Cardiol 2006;113:437–438.CrossRefPubMedGoogle Scholar
  25. 25.
    Quan W, Wu B, Bai Y, Zhang X, Yin J, Xi M, et al. Magnesium lithospermate B improves myocardial function and prevents simulated ischemia/reperfusion injury-induced H9c2 cardiomyocytes apoptosis through Akt-dependent pathway. J Ethnopharmacol 2014;151:714–721.CrossRefPubMedGoogle Scholar
  26. 26.
    Du CS, Yang RF, Song SW, Wang YP, Kang JH, Zhang R, et al. Magnesium lithospermate B protects cardiomyocytes from ischemic injury via inhibition of TAB1-p38 apoptosis signaling. Front Pharmacol 2010;1:111–112.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Quan W, Wei G, Zhou D, Zhu Y, Guo C, Wang Y, et al. Magnesium lithospermate B reduces myocardial ischemia/ reperfusion injury in rats via regulating the inflammation response. Pharm Biol 2013;51:1355–1362.CrossRefPubMedGoogle Scholar
  28. 28.
    Fei AH, Cao Q, Chen SY, Wang HR, Wang FL, Pan SM, et al. Salvianolate inhibits reactive oxygen species production in H(2)O(2)-treated mouse cardiomyocytes in vitro via the TGFß pathway. Acta Pharmacol Sin 2013;34:496–500.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Yang XM, Proctor JB, Cui L, Krieg T, Downey JM, Cohen MV. Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways. J Am Coll Cardiol 2004;44:1103–1110.CrossRefPubMedGoogle Scholar
  30. 30.
    Kim JK, Pedram A, Razandi M, Levin ER. Estrogen prevents cardiomyocyte apoptosis through inhibition of reactive oxygen species and differential regulation of p38 kinase isoforms. J Biol Chem 2006;281:6760–6767.CrossRefPubMedGoogle Scholar
  31. 31.
    Li J, Miller EJ, Ninomiya-Tsuji J, Russell RR, Young LH. AMP-activated protein kinase activates p38 mitogenactivated protein kinase by increasing recruitment of p38 MAPK to TAB1 in the ischemic heart. Circ Res 2005;97:872–879.CrossRefPubMedGoogle Scholar
  32. 32.
    Fiedler B, Feil R, Hofmann F, Willenbockel C, Drexler H, Smolenski A. cGMP-dependent protein kinase type I inhibits TAB1-p38 mitogen-activated protein kinase apoptosis signaling in cardiac myocytes. J Biol Chem 2006;281:32831–32840.CrossRefPubMedGoogle Scholar

Copyright information

© Chinese Association of the Integration of Traditional and Western Medicine and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Jian-yong Qi
    • 1
  • Juan Yu
    • 2
  • Dong-hui Huang
    • 1
  • Li-heng Guo
    • 1
  • Lei Wang
    • 1
  • Xin Huang
    • 1
  • Hai-ding Huang
    • 2
  • Miao Zhou
    • 3
  • Min-zhou Zhang
    • 1
    Email author
  • Jiashin Wu
    • 4
  1. 1.Intensive Care Laboratory, Guangdong Province Hospital of Chinese Medicine2nd Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhouChina
  2. 2.Animal Laboratory, Guangdong Province Hospital of Chinese Medicine2nd Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhouChina
  3. 3.Department of Oral and Maxillary SurgeryStomatology Hospital of Guangzhou Medical UniversityGuangzhouChina
  4. 4.Northeast Ohio Medical UniversityRootstownUSA

Personalised recommendations