Liu Wei, Sui Danjuan, Ye Huanying, Ouyang Zhen, Wei Yuan
School of Pharmacy, Jiangsu University, Zhenjiang, China.
PeerJ. 2019 Apr 23;7:e6807. doi: 10.7717/peerj.6807. eCollection 2019.
Arachidonic acid (AA) is oxidized by cytochrome P450s (CYPs) to form epoxyeicosatrienoic acids (EETs), compounds that modulate ion transport, gene expression, and vasorelaxation. Both CYP2Cs and CYP2Js are involved in kidney EET epoxidation.
In this study, we used a -null rat model to explore the in vivo effects of CYP2C11 on vasorelaxation. For 2 months, -null and wild-type (WT) Sprague-Dawley rats were either fed normal lab (0.3% (w/w) sodium chloride) or high-salt (8% (w/w) sodium chloride) diets. Subsequently, an invasive method was used to determine blood pressure. Next, western blots, quantitative PCR, and immunohistochemistry were used to determine renal expression of CYPs involved in AA metabolism.
Among -null rats, a high-salt diet (females: 156.79 ± 15.89 mm Hg, males: 130.25 ± 16.76 mm Hg, = 10) resulted in significantly higher blood pressure than a normal diet (females: 118.05 ± 8.43 mm Hg, < 0.01; males: 115.15 ± 11.45 mm Hg, < 0.05, = 10). Compared with WT rats under the high-salt diet, western blots showed that -null rats had higher renal expression of CYP2J2 and CYP4A. This was consistent with the results of immunohistochemistry and the qPCR, respectively. The two rat strains did not differ in the renal expression of CYP2C23 or CYP2C24.
Our findings suggested that CYP2C11 plays an important role in lowering blood pressure under the challenge of a high-salt diet.
花生四烯酸（AA）被细胞色素P450（CYP）氧化形成环氧二十碳三烯酸（EET），这些化合物可调节离子转运、基因表达和血管舒张。CYP2C和CYP2J均参与肾脏中EET的环氧化过程。
在本研究中，我们使用基因敲除大鼠模型来探究CYP2C11对血管舒张的体内作用。为期2个月，基因敲除和野生型（WT）Sprague-Dawley大鼠分别喂食正常实验室饲料（0.3%（w/w）氯化钠）或高盐（8%（w/w）氯化钠）饲料。随后，采用侵入性方法测定血压。接下来，使用蛋白质免疫印迹法、定量PCR和免疫组织化学法来测定参与AA代谢的CYP在肾脏中的表达。
在基因敲除大鼠中，高盐饮食（雌性：156.79±15.89毫米汞柱，雄性：130.25±16.76毫米汞柱；n = 10）导致的血压显著高于正常饮食（雌性：118.05±8.43毫米汞柱，P < 0.01；雄性：115.15±11.45毫米汞柱，P < 0.05；n = 10）。与高盐饮食下的WT大鼠相比，蛋白质免疫印迹法显示基因敲除大鼠肾脏中CYP2J2和CYP4A的表达更高。这分别与免疫组织化学和定量PCR的结果一致。两种大鼠品系在CYP2C23或CYP2C24的肾脏表达上没有差异。
我们的研究结果表明，在高盐饮食的挑战下，CYP2C11在降低血压方面发挥着重要作用。
