鞘胺醇1-磷酸2/3受体对心肌缺血再灌注损伤的影响

目的观察鞘胺醇1-磷酸2/3受体(S1PR2/3)在大鼠心肌缺血再灌注的在体实验中对心脏的影响。方法健康SD雄性大鼠,随机分为7组:正常对照组、假手术组、IR组、IR+DMSO组、IR+Cym5541(S1P3受体激动剂)组、IR+Cay10444(S1P3受体阻断剂)组、IR+Cay10444/Jte-013(S1P2/3受体阻断剂)组。制作大鼠缺血再灌注模型,并记录心功能、心肌梗死面积、死亡率。结果给予S1PR3抑制剂组和S1PR2/3抑制剂组与IR组相比在心肌缺血再灌过程中,心率下降(P0.05),左室舒张末期压力(LVEDP)上升(P0.05),心肌梗死面积增大(55.7%:28.8%,51.6%:28.8%),给予S1PR3激动剂组心肌梗死面积显著减小(18.6%:28.8%)。给予S1P2/3抑制剂组死亡率明显高于IR组(53%:22%,P0.05)。结论 S1P2和S1P3受体对缺血再灌注心肌起保护作用,抑制S1P2/3受体参与了IR后心源性猝死(SCD)。

The effect of S1PR2/3 during myocardial ischemia-reperfusion injury

Objective To observe the effect of S1PR2/3 on heart during myocardial ischemia-reperfusion (I/R) in rats. Methods Healthy adult male Sprague-Dawley rats were randomly divided into 7 groups: control group, sham operation group, IR group, IR group treated with DMSO, IR group treated with Cym5541( agonist of S1P3), IR group treated with Cay10444 (antagonist of S1P3), IR group treated with Cay10444/Jte-013 (antagonist both S1P3 and S1P2). In vivo model of myocardial ischemia-reperfusion was established. The hemodynamics, infarction area and mortality was recorded. Results Compared with IR, the S1PR3 antagonist group and S1PR2/3 antagonist group showed signiifcantly reduction of heart rate(HR) and increament left ventricular end-diastolic pressure(LVEDP)(P<0.05). In addition, the infarction area was increased in the S1PR3 antagonist group and S1PR2/3 antagonist treated group (55.7%:28.8%, 51.6%:28.8%), respectively. Treatment with S1PR3 agonist reduced the infarct size compared with IR group(18.6%:28.8%). Blocking S1P2/3 receptors increased IR-induced mortality signiifcantly (53%:22%, P<0.05). Conclusion S1PR2/3 have a beneifcial effect on heart. S1PR2 and S1PR3 were involved in the IR-induced SCD.