白藜芦醇预适应对心脏骤停后大鼠心脏功能的影响

Effect of Resveratrol Preconditioning on Myocardial Dysfunction after Cardiac Arrest in Rats

目的通过研究心脏骤停后自主循环恢复(return of spontaneous circulation,ROSC)后大鼠血流动力学和心肌组织硝化应激,探讨白藜芦醇预适应对ROSC后大鼠心脏功能的影响及其可能的机制。方法 SD大鼠采用经食道交流电刺激致颤的方法诱发心脏骤停,诱发前15min给予干预。获得ROSC的大鼠分为溶剂对照组(不给予药物干预,只给予等体积溶剂),白藜芦醇2.3mg/kg、0.23mg/kg、0.023mg/kg干预组,并设假手术组(不诱发心脏骤停),分别于ROSC后0.5h、1.0h、2.0h、3.0h和4.0h监测血流动力学指标,于ROSC后4h处死实验动物,测定心肌组织诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)蛋白表达、心肌组织过氧化亚硝酸盐水平和心肌组织硝基酪氨酸盐含量。结果 1采用经食道交流电刺激法诱发心脏骤停成功率100%,总的ROSC率72.7%。白藜芦醇组大鼠ROSC率无显著提高。2各干预组ROSC后早期心率、血压下降,随后心率逐渐上升,接近基线值,血压仍进行性下降。白藜芦醇对血压、心率无显著影响。3ROSC后各组心功能呈下降趋势,白藜芦醇可明显改善心脏功能,其中白藜芦醇0.23mg/kg和0.023mg/kg组改善最显著。4ROSC后心肌iNOS表达、过氧化亚硝酸盐含量、硝基酪氨酸盐含量明显升高,白藜芦醇组明显下降,低浓度组较高浓度组更明显。结论ROSC后大鼠心脏功能下降,白藜芦醇干预后心脏功能明显改善,此效应可能与其抑制心肌硝化应激有关。

Objective To investigate the protective effects and its potential mechanism of resveratrol preconditioning on rat cardiac arrest after return of spontaneous circulation（ROSC）with the study of hemodynamic parameters and nitrative stress in myocardium.Methods Cardiac arrest SPF SD rat model was established by transoesophageal cardiac alternating current stimulation.Intervention was implemented 15 min before cardiac arrest.Twenty four rats with ROSC after cardiac arrest were randomly assigned into five groups：vehicle,sham,resveratrol 2.3mg/kg（A group）,resveratrol 0.23 mg/kg（B group）and resveratrol 0.023 mg/kg（C group）.Heart rate,mean arterial pressure,and left ventricular variables（＋dp/dtmax and-dp/dtmin）were recorded in0.5h,1.0h,2.0h,3.0h,and 4.0hrespectively.Rats were sacrificed at 4hafter ROSC,and hearts were removed for determining expression of inducible nitric oxide synthase（iNOS）protein,myocardial peroxynitrite,and nitrotyrosine.Results Global ROSC rate was 72.7% after the induction of cardiac arrest. Resveratrol preconditioning did not improve ROSC rate significantly.Heart rate and blood pressure declined at early phase of ROSC,then heart rate recovered to the baseline value,but blood pressure still declined progressively.There were no significant differences between resveratrol groups and vehicle group.Myocardial function worsened progressively even after ROSC.Resveratrol improved cardiac function significantly,especially in lower concentration groups.Myocardial iNOS expression,peroxynitrite,and nitrotyrosine content increased significantly after ROSC.Resveratrol decreased these products significantly,and lower concentration groups did better.ConclusionResveratrol preconditioning could improve cardiac dysfunction after ROSC,which may be associated with its inhibitory effect on nitrative stress.