全反式维甲酸对高血压大鼠体内apelin-APJ信号系统的影响

Effects of all-trans retinoic acid on the apelin-APJ signaling in spontaneously hypertensive rats

目的:探讨全反式维甲酸(atRA)对高血压大鼠体内心血管活性多肽apelin及其受体APJ信号的影响。方法:采用12周龄雄性自发性高血压大鼠(SHR)及其同源对照WKY大鼠,经腹腔注射atRA,为期1月。分别用实时荧光定量多聚酶链式反应(PCR)与免疫印迹技术测定atRA治疗后SHR体内apelin和APJ受体的表达情况。结果:与WKY对照组相比,SHR心脏组织中apelin及其受体APJ的 mRNA和蛋白表达明显下调(P均<0.01)。而atRA治疗后SHR(低、高剂量atRA组)大鼠心脏组织中apelin、APJ表达出现上调(P均<0.05)。结论:长期atRA治疗促进SHR大鼠心脏组织中apelin及其受体APJ的表达增加,提示转录调节剂atRA很可能对人类高血压病防治具有积极作用。

Objective： apelin, a newly identified angiotensin （Ang） Ⅱ homologue, has been shown to act as an endogenous ligand of the orphan receptor APJ and implicated in essential hypertension, apelin can regulate blood pressure through antagonizing of Ang Ⅱ actions and potentiating of nitric oxide （NO） release. The aim of the present study is to explore effects of all-trans retinoic acid （atRA） on the apelin-APJ signaling in hypertension. Methods： Twelveweek-old male spontaneously hypertensive rats （SHR） were treated with atRA given as daily intraperitoneal injection for one month; age- and sex-matched Wistar-Kyoto （WKY） rats and placebo-treated SHR served as controls. Realtime PCR and Western blot were performed to examine mRNA and protein expressions of apelin and its receptor APJ in rats after atRA treatment. Results： In placebo-treated SHR, mRNA and protein expressions of apelin and APJ receptor were markedly depressed compared with WKY rats （P〈0.01, respectively） . However, in atRA-treated SHR, significant up-regulations of apelin and APJ receptor expressions were observed in heart （P〈0.05, respectively）. Conclusion： Chronic atRA treatment contributes to enhancements of cardiac apelin and APJ receptor in SHR. Thus, atRA, as a transcription-modulating drug, may have potentially clinical values in the prevention and treatment of human essential hypertension. Author＇s address：