The Study Of The Protective Effects Of Sodium Tanshinone â…¡A Sulfonate For Myocardial Ischemia Reperfusion Injury In Rats

Objective: Reperfusion will lead to ischemia area expanding, no-reflow, myocardialstuning and reperfusion arrhythmia. So low blood pressure, heart disfunction,arrhythmia and sudden death represent in clinic. Today more and more researcherspay attention to reperfusion injury because of the development of thrombolysis andintervention technology. But until now the mechanism of reperfusion is still notclearly. Recently, several studies have reported renin-angiotensin system(RAS) isconcerned with reperfusion injury. Angiotensinâ…¡will increase in cardiac tissue whenischemia occurr, and then Ca²⁺ inflow from ecto-cellular, that lead to Ca²⁺ over-loadintra-cellular, reperfusion injury and arrhythmia. Meanwhile mRNA expression of AT₁and AT₂ receptor increase. As we all know AT₁ receptor can enhance contraction ofcoronary artery and myocardium, and AT₂ receptor can active bradykinin/NO/cGMPsystem which can protect heart function. Sodium tanshinoneâ…¡A sulfonate(STS) is thewater-solubility derivation of tanshinoneâ…¡A, it can block Ca²⁺ channel, removeoxygen free radical and anti-inflammation. Some reports have showed STS canprotect myocardium in reperfusion. In that purpose we established isolated heartmodel of reperfusion in rats and add low and high dose of STS in perfusionsolution.We had observed and recorded heart rate, coronary flow, incidence rate andduration of ventricle tachycardia and ventricle fibrillation. We also had measured themRNA expression of AT₁ and AT₂ receptor, Angâ…¡and aldosterone level in ischemicmyocardium in order to discuss STS protection function and mechanize in moleculelevel.Methods: The model of ischemia/reperfusion on isotated heart was produced byligation the left anterior descending coronary artery in healthy Wistar rats of male, andreperfused after 10 minutes. Rats were randomized to control group(sham-operationgroup,Krebs-Henseleit solution perfused 120 min,n=8), ischemia reperfusiongroup(ligated the left anterior descending coronary artery 10 min, reperfused 120 minby K-H solution,n=8),low dose of STS group (ligated the left anterior descending coronary artery 10 min, reperfused 120 min by 20mg/L of STS in K-H solution, n=8),high dose of STS (ligated the left anterior descending coronary artery 10 min,reperfused 120 min by 40mg/L of STS in K-H solution,n=8) We observed andrecorded rate,rhythm and coronary flow of the isolated heart.We also recorded thetime of ventricular tachycardia and fibrillation.The gene expression of angiotensinâ…¡type 1 receptor and type 2 receptor were measured by reversetranscription-polymerase chain reaction(RT-PCR)method. The activities of cardiacmuscle angiotensionâ…¡and aldo were examined by the method ofradioimmunoassay test.Result: 1. There was no significant differences among the four groups at the time ofpre-ligation, after ligation 10min, reperfusion 5min, 30min, 60min and 120min. 2.Coronary flow was lower significantly in group B than group A (P＜0.05)at the time ofafter ligating 10min, reperfusion 5min, 30min, 60min and 120min. group C washigher than group B(P＜0.05) at the time of reperfusion 5min, 30min, 60min and120min. group D was higher than group B at the time of 120min afterreperfusion(P＜0.05), but show no difference at other time. 3. Incidence rate and timeof ventricle tachycardia and ventricle fibrillation in group C and D dramaticdecrease than group B. Group C was lower than group D. 4. In the ischemia area,theexpression of AT₁mRNA and AT₂mRNA enhanced in group B, C and D . Theexpression of AT₁mRNA in group C and D depressed than group B(P＜0.01). there wasno difference in group B and C of AT₂mRNA, but group D was significant lower thangroup B and C. 5.The level of Angâ…¡in myocardium was increased in group B thangroup C and D, but no difference in group C and D. 6. The level of adlosterone ingroup C and D were higher than group B in cardiac tissue.Conclusion: 1. There is no effection in heart rate when ischemic reperfusionmyocardium treated by STS. 2. STS can increase coronary flow and low doserepresent significant adventage than high dose. 3. STS can dramatic decreaseincidence rate and duration of ventricle tachycardia and ventricle fibrillation. 4. STS can depress AT1mRNA expression, low dose STS can up-regulation AT₂/AT₁, this. ismaybe the reason of heart protection. 5. STS can decrease the level of Angâ…¡inischemic reperfusion myocardium. 6. STS can decrease the level of ALD in ischemicreperfusion myocardium. 7. Low dose of STS is better than high dose aboutimproving coronary flow, protecting reperfusion arrhythmia, enhancing mRNAexpression of AT₂ receptor and depressing Angâ…¡and ALD level.