20-HETE对大鼠心肌缺血再灌注损伤中NADPH氧化酶活性及ROS生成的影响

目的探讨20-HETE加重大鼠离体心肌缺血再灌注损伤的作用及机制。方法雄性Wistar大鼠随机分为正常对照组（Con组）,缺血再灌注模型组（IR组）,IR+20-HETE合成酶抑制剂（HET0016）组,Con+HET0016组,每组12只,通过Langendorff灌流系统建立大鼠离体心肌缺血再灌注模型,全心缺血35 min再灌注40 min,Power Lab/8P系统实时监测心肌力学指标;灌流结束后取心肌组织TTC法检测心肌梗死面积;DHE荧光探针法检测活性氧簇（reactive oxygen species,ROS）含量;Western blot检测NADPH氧化酶亚基p47^phox磷酸化水平;细胞色素C的还原法检测NADPH氧化酶活性。结果离体心脏缺血再灌注后,加入20-HETE合成酶抑制剂HET0016（1μmol/L）后明显改善了IR导致的心肌力学指标下降,LVDP由IR组的（48.6±3.4）%升至（71.7±3.5）%,+d P/dt_max由（51.9±2.1）%升至（69±3.2）%,-d P/dt_max由（47.1±3.6）%升至（64.1±3.8）%（P<0.05）;IR+HET0016组心肌梗死面积比IR组减小了37.2%（P<0.05）。DHE荧光探针检测发现IR+HET0016处理组心肌组织中ROS含量比IR组降低了45.8%（P<0.05）;最后通过对NADPH氧化酶活性检测发现,HET0016显著减少了IR引起的NADPH氧化酶p47^phox亚基磷酸化水平及全酶活性的升高（P<0.05）。结论 20-HETE通过激活NADPH氧化酶诱导过量ROS的生成,加重心肌缺血再灌注损伤。     

20-HETE作用受体的发现及其对高血压的影响

20-Hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoactive eicosanoid discovered in recent years, which has multiple vascular effects including stimulation of smooth muscle contractility, migration, and proliferation, as well as endothelial cell dysfunction and inflammation. Clinical and experimental research suggests that 20-HETE is an important mediator of cardiovascular function, and plays a critical role in the pathogenesis of hypertension, stroke, myocardial infarction and vascular diseases. Recently, G-protein-coupled receptor 75 (GPR75) was identified as a 20-HETE receptor and mediated the development of 20-HETE-dependent hypertension. The discovery of 20-HETE-GPR75 pairing provides the molecular basis for the signaling and pathophysiological functions mediated by 20-HETE in hypertension and cardiovascular diseases. In this brief review, we discuss the recent findings related to the effects of 20-HETE in the pathogenesis of hypertension and the discovery and effects of GPR75.