Abstract： Objective To observe the expression changes of microRNA 1 （miRNA-1） and microRNA 21（miRNA-21） after ischemic preconditioning （IPC）, ischemic postconditioning （IPO） and remote ischemic preconditioning （RIPC）in an ischemia-reperfusion rat heart model in vitro, as well as the expression of their target protein heat shock protein 70 （HSP70） and programmed cell death 4 （PDCD4）, and evaluate whether miRNA are involved in endogenous cardio-protective mechanism. Methods The Langendorff-perfused Sprague-Dawley rat hearts were randomly assigned into one of the four groups, control group （CON group, n=12）, ischemia preconditioning group （IPC group， n=12） , ischemia postconditioning group （IPO group， n=12） and remote ischemia preconditioning group （RIPC group，n=12）. Cardiac function was digitalized and analyzed. The expression of HSP70, PDCD4, B-cell lymphoma/leukemia-2 （Bcl-2） and Bax was detected by Western blotting. The expression of miRNA-1 and miRNA-21 was detected by real-time reverse transcriotion-polymerase chain reaction （RT-PCR）. Assessment of cardiac infarct size and myocardial apoptosis was determined using triphenyltetrazolium chloride （TTC） assay and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay （TUNEL） assay respectively. Results The expressions of miRNA-1 and miRNA-21 were up-regulated in IPC group, but the expression of miRNA-1 was down-regulated in RIPC group and IPO group （P＜0.05）. The expressionsof PDCD4, HSP70 and Bax were down-regulated in ‘conditioning’ groups compared with CON group （P＜0.05）. The expression of Bcl-2 was not statistically different among the four groups. The infarct size and the myocardial apoptosis in ‘conditioning’ hearts were significantly decreased compared with CON group （P＜0.05）. Conclusion The expressions of the miRNA-1 and miRNA-21 are different in IPC, RIPC and IPO groups, and their target proteins are not inversely correlated with the miRNAs in all the ‘conditioning’ groups.
Citation：
DUAN Xin,WANG Xiaohua,JI Bingyang,LIU Jinping,LONG Cun.. Expression of MicroRNA-1, 21 in Ischemic Preconditioning, Ischemic Postconditioning and Remote Ischemic Preconditioning in an Isolated Rat Heart Model. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2012, 19(4): 402-406. doi:
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- 1. Cardiovasc Res， 2001，51 （4）：637-646.
- 2. Hausenloy DJ， Yellon DM. The evolving story of “conditioning” to protect against acute myocardial ischaemia-reperfusion injury. Heart， 2007， 93 （6）：649-651.
- 3. Murry CE， Jennings RB， Reimer KA. Preconditioning with ischemia： a delay of lethal cell injury in ischemic myocardium. Circulation， 1986， 74 （5）：1124-1136.
- 4. Zhao ZQ， Corvera JS， Halkos ME， et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion： comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol， 2003， 285 （2）：H579-588.
- 5. Przyklenk K， Bauer B， Ovize M， et al. Regional ischemic ′preconditioning′ protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation， 1993， 87 （3）：893-899.
- 6. Gho BC， Schoemaker RG， van den Doel MA， et al. Myocardial protection by brief ischemia in noncardiac tissue. Circulation， 1996， 94 （9）：2193-2200.
- 7. Pell TJ， Baxter GF， Yellon DM， et al. Renal ischemia preconditions myocardium：role of adenosine receptors and ATP-sensitive potassium channels. Am J Physiol， 1998， 275 （5 Pt 2）：H1542-1547.
- 8. Kharbanda RK， Mortensen UM， White PA， et al. Transient limb ischemia induces remote ischemic preconditioning in vivo.Circulation， 2002，106 （23）：2881-2883.
- 9. Bushati N， Cohen SM. microRNA functions. Annu Rev Cell Dev Biol， 2007， 23 （1）：175-205.
- 10. Chang TC， Mendell JT. microRNAs in vertebrate physiology and human disease. Annu Rev Genomics Hum Genet， 2007， 8：215-239.
- 11. Yin C， Salloum FN， Kukreja RC. A novel role of microRNA in late preconditioning： upregulation of endothelial nitric oxide synthase and heat shock protein 70. Circ Res， 2009，104 （5）：572-575.
- 12. Cheng Y， Zhu P， Yang J， et al. Ischaemic preconditioning-regulated miR-21 protects heart against ischaemia/reperfusion injury via anti-apoptosis through its target PDCD4. Cardiovasc Res，87 （3）：431-439.
- 13. Hausenloy DJ， Tsang A， Yellon DM. The reperfusion injury salvage kinase pathway： a common target for both ischemic preconditioning and postconditioning. Trends Cardiovasc Med， 2005，15 （2）：69-75.
- 14. Wang Y， Xu H， Mizoguchi K， et al. Intestinal ischemia induces late preconditioning against myocardial infarction： a role for inducible nitric oxide synthase. Cardiovasc Res， 2001，49 （2）：391-398.
- 15. Kuntscher MV， Kastell T， Altmann J， et al. Acute remote ischemic preconditioning II： the role of nitric oxide. Microsurgery， 2002，22 （6）：227-231.
- 16. Xu C， Lu Y， Pan Z， et al. The muscle-specific microRNAs miR-1 and miR-133 produce opposing effects on apoptosis by targeting HSP60， HSP70 and caspase-9 in cardiomyocytes. J Cell Sci， 2007，120 （Pt 17）：3045-3052.
- 17. Kwon C， Han Z， Olson EN， et al. MicroRNA1 influences cardiac differentiation in Drosophila and regulates Notch signaling. Proc Natl Acad Sci U S A， 2005，102 （52）：18986-18991.
- 18. Chen JF， Mandel EM， Thomson JM， et al. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet， 2006，38 （2）：228-233.
- 19. Heusch G， Boengler K， Schulz R. Cardioprotection： nitric oxide， protein kinases， and mitochondria. Circulation， 2008，118 （19）：1915-1919.
- 20. Latchman DS. Heat shock proteins and cardiac protection.
- 21. Hampton CR， Shimamoto A， Rothnie CL， et al. HSP70.1 and -70.3 are required for late-phase protection induced by ischemic preconditioning of mouse hearts. Am J Physiol Heart Circ Physiol， 2003，285 （2）：H866-874.
- 22. Wang G， Liem DA， Vondriska TM， et al. Nitric oxide donors protect murine myocardium against infarction via modulation of mitochondrial permeability transition. Am J Physiol Heart Circ Physiol， 2005，288 （3）：H1290-1295.
- 23. Precht TA， Phelps RA， Linseman DA， et al. The permeability transition pore triggers Bax translocation to mitochondria during neuronal apoptosis. Cell Death Differ， 2005，12 （3）：255-265.
- 24. Schmitt JP， Schroder J， Schunkert H， et al. Role of apoptosis in myocardial stunning after open heart surgery. Ann Thorac Surg， 2002，73 （4）：1229-1235.
- 25. Penna C， Tullio F， Merlino A， et al. Postconditioning cardioprotection against infarct size and post-ischemic systolic dysfunction is influenced by gender. Basic Res Cardiol， 2009，104 （4）：390-402.
