腺苷A3受体(A3AR)在失血性休克血管反应性调节中的作用

目的： 阻力血管对血管活性物质反应性的降低是决定创伤休克发生、发展及预后的重要因素。腺苷是机体遭受创伤、缺氧时大量释放的重要内源性调质，并通过相应受体发挥作用。本研究拟观察腺苷A3受体(A3AR)在失血性休克大鼠肠系膜上动脉的表达变化情况及其与休克血管反应性变化间的关系，初步探讨A3AR是否参与对休克血管反应性的调节。方法：参照以往的工作基础，建立大鼠失血性休克(40 mmHg)模型；大鼠肠系膜上动脉对缩血管物质去甲肾上腺素(NE)诱导的收缩反应性采用离体小血管张力测定仪检测；A3AR的蛋白及mRNA表达变化情况分别采用Western blotting及RT-PCR进行检测。结果：结果显示，在大鼠失血性休克后0-4 h，其肠系膜上动脉1-2级分支血管对由NE诱导的收缩反应性呈现“双向性”变化；A3AR mRNA表达随休克时间的延长呈逐渐降低的趋势，但无显著差异；而肠系膜上动脉血管平滑肌A3AR的蛋白表达在休克后即刻呈增加趋势，随着休克时间的延长，其表达逐渐下降，尤其以休克后4h的表达下降最为明显；此外，A3AR激动剂可部分恢复休克2 h大鼠肠系膜上动脉对NE的收缩反应性，且该作用可被A3AR阻断剂MRS1523所拮抗。结论：A3AR参与失血性休克血管低反应性的形成，在失血性休克后激动A3AR受体可保护血管功能，部分恢复失血性休克后大鼠阻力血管对NE的收缩反应性。

Role of A3 adenosine receptor on vascular reactivity of superior mesenteric artery in hemorrhagic shock in rat

AIM: To explore whether A3 adenosine receptor plays a role in the modulation of vascular reactivity after hemorrhagic shock in rat, and to find out the prospective drug target to restore the decreased vascular reactivity following hemorrhagic shock. METHODS: The hemorrhagic shock (40 mmHg) model was established in rat, and the reactivity of superior mesenteric artery (SMA) to norepinephrine (NE) was observed. A3AR expression at protein level and mRNA level were measured by Western blotting and RT-PCR respectively. RESULTS: The vascular reactivity of SMA to NE after hemorrhagic shock (40 mmHg) was decreased significantly in a biphasic response manner. The expression of A3AR mRNA in SMA after hemorrhagic shock decreased without significant difference. The expression of A3AR protein has a slight increase without statistical difference after 30 min of hemorrhagic shock and then has a significant decrease (especially at 2 h and 4 h after hemorrhagic shock). The usage of IB-MECA, a selective A3AR agonist, significantly increased the responsiveness of SMA to NE in hemorrhagic shock in rat. MRS1523, the selective A3AR antagonist, significantly abolished the restoration of the vascular reactivity to NE by IB-MECA in hemorrhagic shock in rat. CONCLUSION: A3AR plays a role in the modulation of vascular responsiveness to NE in hemorrhagic shock in rat, and the selective agonist of A3AR could restore the reactivity of SMA to NE in hemorrhagic shock in rat.