Experimental Studies Of Taxifolin's Effect On The Acute Myocardial Ischemia-reperfusion Injury In Rats

Objective: To study the taxifolin's effect on acute myocardium ischemia-reperfusion in rats and the possible mechanisms.Methods: Wistar male rats were randomly and evenly divided into five groups: sham-operated group(S); model control group(C); taxifolin-treated low-dose group(L); taxifolin-treated high- dose group(H) ; ischemic preconditioning group(I). Established in rats with acute myocardial ischemia-reperfusion model, S group handled thoracotomy but did not occluded coronary artery; the left anterior descending coronary artery was occluded for 30 min followed 2 h reperfusion in the four other groups. S group was given PBS 0.1ml through external jugular vein; C and I groups were given PBS besides L and H groups were respectively given taxifolin 0.5μg*kg-1,5μg*kg-1 before reperfusion using the same way and the same volume as S group; I group was given left anterior descending coronary artery 5 min ischemia and 5 min reperfusion two cycles then 5 min ischemia and 10 min reperfusion a round before ischemia reperfusion. ECG and Hemodynamics were monitored during the period of ischemia and reperfusion. The area of myocardium at risk and infarct size were delineated by Evan's blue and triphenyltetrazolium chloride(TTC) staining. myeloperoxidase(MPO) activity were measured in injured tissues. The activity of CK and the content of TNF-αwere measured in blood serum. Using immunohistochemical staining of the SABC to measure the expression of ICAM-1 and NF-κB and determinate the ICAM-1 mRNA expression by RT-PCR in myocardial tissue.Results: After two hours of reperfusion, in comparison with group S, the value of LVSP and±dp/dtmax were reduced and the activity of MPO and CK as well as the yield of TNF-αand MDA were all markedly increased in group C, and the expression of ICAM-1,NF-κB,ICAM-1 mRNA were all also markedly increased. Compared with group C, in groups L,H and I , the descent of hemodynamics was improved as well as the increase of MPO,CK and TNF-α,MDA were decreased remarkably; The infarct sizes and the expression of ICAM-1,NF-κB,ICAM-1 mRNA were also decreased markedly. There was no obvious difference between groups L and I but with obvious difference between groups H and I also H and L.Conclusion: Taxifolin may plays its role through its antioxidant activity such as the destruction of reactive oxygen species so stops the activation of NF-κB, thereby inhibits the cytokine TNF-αand inhibits the expression of ICAM-1 on myocardial cells and so limits leucocyte accumulation and the inflammatory response thus plays a remarkable protective effect on ischemia-reperfusion injury.