1-磷酸鞘氨醇后适应对大鼠心肌缺血/再灌注损伤的保护作用

Protective effect of sphingosine 1-phosphate postconditioning on myocardial ischemia reperfusion injury in rats

目的观察1-磷酸鞘氨醇(sphingosine 1-phosphate,S1P)后适应对大鼠心肌缺血/再灌注损伤的保护作用。方法采用结扎冠状动脉左前降支(LAD)缺血30 min/再灌120 min的方法建立在体大鼠心肌缺血/再灌注损伤模型。60只大鼠随机分为5组(每组12只),即①假手术组(sham group);②缺血/再灌注组(I/R group);③S1P 0.5 mg·kg-1;④S1P 1 mg·kg-1;⑤S1P 2 mg·kg-1剂量组。四氮唑染色法观察心肌梗死面积;ELISA法测定血浆肌酸激酶同工酶(CK-MB)活性;比色法测定血浆丙二醛(MDA)、髓过氧化物酶(MPO)含量;光学显微镜及透射电子显微镜技术观察心肌组织形态学变化。结果与I/R组比较,S1P 0.5、1、2 mg·kg-1可降低心肌梗死面积(P<0.05),降低血浆CKMB活性(P<0.01)及MPO含量(P<0.05,P<0.01,P<0.01)。S1P 1、2 mg·kg-1可降低血浆MDA水平(P<0.01)。并可改善心肌坏死、炎细胞浸润、组织水肿以及线粒体损伤程度。结论 S1P后适应对大鼠心肌缺血/再灌注损伤具有保护作用,该作用可能与抑制炎症反应、拮抗氧化应激、保护线粒体结构功能有关。

Aim To study the protective effect of sphingosine 1-phosphate （SIP） postconditioning on myocardial ischemia/repeffusion injury in rats. Meth- ods Rat model of myocardial ischemia reperfusion in- jury was established by occluding the left anterior de- scending coronary artery for 30min then reperfusing for 120min. Sixty rats were randomly divided into 5 groups （ 12 rats in each group） ： （ 1 ） sham group, （2） ischemia/reperfusion group （ I/R group）, （ 3 ） S1P 0. 5 mg ·kg^-1,（4） SIP 1 mg ·kg^-1,and （5） SIP2 mg·kg^-1 group. The size of infarct area was determined by tetrazolium staining method. ELISA method was used to measure plasma CK-MB. Plasma MDA, MPO was measured by colorimetric method. To observe histomor- phology change of myocardium, light microscope and electron microscope were used. Results Compared with I/R group, SIP 0.5,1,2 mg ·kg^-1 could de- crease myocardial infarct size （ P 〈 0.05 ） , lower plas- maCK-MB （P 〈0.01） and MPO （P 〈0.05,P 〈 0.01,P〈0.01）. SIP 1,2 mg ·kg^-1 could reduce plasma MPO （ P 〈 0. 01 ）. Microscope study showed SIP could improve myocardial necrosis, and relieve neutrophil infilitration, tissue edema and mitochondrial damage. Conclusion SIP posteonditioning can pro- tect against myocardial ischemia/reperfusion injury, which may be related to the inhibition of inflammation, antioxidation, and mitochondrial protection.