花生四烯酸细胞色素P450表氧化酶在自发性高血压大鼠血压的调节中的作用

背景与目的花生四烯酸细胞色素P450（CYP）表氧化酶代谢花生四烯酸产生表氧化廿烷酸（EETs），又称为内皮源性超极化因子（EDHFs），在局部微循环的调节中起着重要作用。然而EETs在血压的调节中是否起作用还不清楚。本研究通过对成年自发性高血压大鼠导入花生四烯酸细胞色素表氧化酶基因来观察其血压变化，从而进一步明确EETs在血压调节中的作用。方法：将含人类细胞色素P450表氧化酶CYP2J2 cDNA的真核细胞表达质粒pcDNA．2J2经静脉注射（3mg／kg）人雄性成年自发性高血压大鼠，并以pcDNA3．1对照。然后用尾部血压计测量血压。并在注射后3周和4周时处死动物，检测CYP2J2在不同组织中的表达情况。结果：注射质粒后对照组血压一直无显著性变化，而pcDNA．2J2治疗组大鼠血压显著降低（P〈0．05），这一降压效应持续两周以上。Western blotting显示在实验组动物肺、肝和肾的总蛋白中通过特异性抗-CYP2J2抗体可检测出显著量的人类CYP2J2蛋白的表达。结论：本实验显示对成年自发性高血压大鼠导人人类CYP2J2基因，使CYP2J2可以在动物组织中高表达，从而引起相对持久的降压作用，这些结果提示花生四烯酸细胞色素P450表氧化酶通过产生EDHFs参与了动物血压的调节作用。

The Role of Arachidonic Acid Cytochrome P450 Epoxygenases in the Regulation of the Blood Pressure in Spontaneous Hypertesive Rats

Background and purposes:Arachidonic acid cytochrome P450 (CYP) epoxygenases metabolize arachi-donic acid to produce Epoxyeicosatrienoic acids (EETs), also named endothelium-derived hyperpolarizing factors (EDHFs). It has demonstrated that EETs or EDHFs play an important role in the regulation of local microcirculation. Their regulatory effect on blood pressure, however, is unknown or controversial. The present study was designed to investigate the effects of delivery of arachidonic acid CYP epoxygenases gene on blood pressure in adultspontaneous hypertensive rats (SHRs) to insight whether the CYP epoxygenases or EDHFs play a role in blood pressure regulation. Method: Mammalian expression vector containing human cytochrome P450 epoxygenase CYP2J2 cDNA (1.5Kb), pcDNA-2J2 and pcDNA3.1 ware intravenously injected into adult spontaneously hypertensive rats, respectively, and then the blood pressure was measured twice a week using rat tail cuff sphygmomanometer until sacrifice at 3 or 4 weeks after the injection. The expression of CYP2J2 in various organs was detected by Western blotting. Result:The intravenous delivery of pcDNA.2J2 induced decrease in blood pressure in SHR compared with control group, and the hypoten-sive effect maintained 2-3 weeks. Western blotting showed detectable expression of human CYP2J2 in lung, live, heart and kidney detected by anti-human CYP2J2 antibodies. Conclusion: The present study showed that the delivery of human CYP2J2 gene induced the high CYP2J2 expression in the animal organs and caused a long-term reduction in blood pressure in SHRs simultaneously, which suggested that arachidonic acid cytochrome P450 epoxygenases involve in the regulation of the blood pressure in SHRs.