1-磷酸鞘氨醇(S1P)在心室重塑过程中对梗死区血流恢复及血管新生的作用研究

Role of sphingosine-1-phosphate (S1P) on the recovery of blood flow and angiogenesis in the infarcted area during ventricular remodeling

目的观察不同时间周期大鼠心肌梗死模型心肌组织中1-磷酸鞘氨醇(S1P)受体在梗死区的基因表达情况,探讨其在心肌梗死后心室重塑过程中对梗死区血流恢复及血管新生的作用。方法采用结扎左冠状动脉前降支(LAD)的方法,造成大鼠左室大面积心梗,建立大鼠心肌梗死模型,分别于术后6、12、24 h观察心肌梗死后心室重塑过程中血流的变化情况。然后处死大鼠,取其心肌组织,提取组织中的RNA,采用实时定量荧光技术(PCR)测定心肌组织中S1P受体mRNA在梗死区的表达情况。结果术后6 h,大鼠心肌血流量和心肌微血管壁通透性随时间节点的增加均明显降低;术后12 h,这种趋势趋缓。术后6 h,S1P1受体mRNA的表达水平呈明显下降趋势;与对照组相比,结扎梗死大鼠梗死区的S1P2受体mRNA在术后各时间节点表达水平均明显下降。术后6 h,结扎梗死大鼠梗死区的S1P3受体mRNA表达显著增强,但术后12 h出现较为明显的表达抑制现象。结论大鼠心肌梗死后的心肌血流恢复和新生血管早期可能与S1P1受体mRNA下调有关,随后与S1P2受体mRNA、S1P3受体mRNA逐渐上调有关。

Objective To observe the gene expression of sphingosine-1-phosphate（S1P） receptors in myocardial tissues after myocardial infarction in rats,and to explore its effect on the recovery of blood flow and angiogenesis during ventricular remodeling after myocardial infarction.Methods Ligation of the left anterior descending coronary artery（LAD） was used to cause large area of myocardial infarction in rats＇ s left ventricule,so as to establish a rat model of myocardial infarction.The change in blood flow during the myocardial infarctio ventricular remodeling process was observed at 6 h,12 h and 24 h after operation.The rats were killed,and the RNA in myocardial tissue was extracted.The expression of S1 P receptor mRNA in myocardial tissue in the infarcted area was detected by using real-time quantitative RNA technology（PCR）.Results The myocardial blood flow and the permeability of myocardial microvascular wall decreased at 6 h after operation.At 12 h after operation,the decreased tendency was slowed down.The expression level of S1P1 receptor mRNA decreased obviously in the infarcted area at 6 h after operation.Compared with normal group,the expression of S1P2 receptor mRNA decreased at each time point after operation.The expression of S1P3 receptor mRNA was significantly enhanced in the infarcted area at 6 h after operation,but it was inhibited at 12 h after operation.Conclusion The recovery of myocardial blood flow and angiogenesis may be related to down-regulating the expression of S1P1 receptor mRNA in the early stage of myocardial infarction in rats,and up-regulating the expression of S1P2 receptor mRNA and S1P3 receptor mRNA gradually in the later stage.