摘要
血管紧张素Ⅱ 1A受体(angiotensin Ⅱ type 1A receptor, AT1aR)是Ang Ⅱ的主要受体亚型。AT1aR基因(Agtr1a)启动子区DNA甲基化水平的变化是调控AT1aR表观遗传的重要机制。为明确运动是否通过调节Agtr1a基因启动子区甲基化水平而减弱ACE1-AT1R收缩轴功能,从而起到改善高血压血管功能的作用,本研究选用3月龄自发性高血压大鼠(spontaneously hypertensive rat, SHR)和正常血压对照组大鼠(Wistar-Kyoto, WKY),随机分为正常血压安静组WKY-C、正常血压有氧运动组WKY-E、高血压安静组SHR-C、高血压有氧运动组SHR-E,各组n=24。12周跑台运动结束后,有氧运动显著减低运动组大鼠血压和体重(P<0.05);采用微血管环张力测定技术测定肠系膜动脉对去甲肾上腺素(norepinephrine, NE)、血管紧张素Ⅱ(angiotensin Ⅱ, Ang Ⅱ)的反应性。结果显示,有氧运动显著减弱高血压大鼠肠系膜动脉对血管收缩因子NE、AngⅡ的收缩反应(P<0.05);高效液相色谱法(high performance liquid chromatography, HPLC)测定血浆中ACE1-AT1R收缩轴主要活性肽血管紧张素原(angiotensinogen, AGT)、AngⅡ的水平。结果显示,有氧运动显著减弱高血压大鼠肠系膜动脉对血管收缩因子NE、AngⅡ的收缩反应(P<0.05);免疫印迹法和q-PCR技术测定肠系膜动脉ACE1、AT1R蛋白质和AT1aR的mRNA水平相对含量。结果显示,有氧运动显著降低高血压大鼠肠系膜动脉ACE1、AT1R蛋白质和AT1aR mRNA水平(P<0.05);亚硫酸氢盐测序BSP法测定Agtr1a基因的启动子区甲基化水平。结果显示,有氧运动显著上调高血压大鼠肠系膜动脉Agtr1a基因启动子区甲基化水平(P<0.05)。本研究表明,有氧运动通过上调高血压肠系膜动脉Agtr1a基因启动子区甲基化水平,即而减弱RAS系统ACE1-AT1R收缩轴功能,从而抑制高血压血管张力增高,缓解血压增高。
The Angiotensin type 1 A receptor(AT1 aR) isoform is more important than AT1 bR in the regulation of blood pressure. The level of AT1 aR methylation is an important mechanism of regulating AT1 R expression. Exercise reduces the expression and function of major molecules of RAS in spontaneously hypertensive rats(SHR). To investigate whether exercise-associated Agtr1a methylation improves the function of the angiotensin-converting enzyme 1(ACE1)-AT1 R vasoconstrictor axis in mesenteric arteries from SHR, three-month-old SHR and age-matched Wistar-Kyoto(WKY) rats were used in this study, and randomly divided into the normotensive control group(WKY-C), the normotensive exercise group(WKY-E), the hypertensive control group(SHR-C), and the hypertensive exercise group(SHR-E), with n=24 in each group. The exercise groups were put to a moderate-intensity treadmill running during 12 weeks. After 12 weeks, aerobic exercise effectively reduced blood pressure and body weight in each group(P<0.05);using vascular tone measurement, the results suggested that aerobic exercise significantly reduced the contractile response of mesenteric arteries to vasoconstriction factors norepinephrine(NE) and Ang Ⅱ in SHR(P<0.05);HPLC results suggested that aerobic exercise significantly reduced the plasma angiotensinogen(AGT) and Ang Ⅱ levels in SHR(P<0.05);Western blotting and qPCR results suggested that aerobic exercise significantly reduced the plasma angiotensinogen(AGT) and Ang Ⅱ levels in SHR(P<0.05);bisulfite sequencing PCR results suggested that aerobic exercise significantly upregulated the methylation level of the Agtr1a promoter region in mesenteric arteries from SHR(P<0.05). These results suggest that aerobic exercise-associated Agtr1a methylation attenuates the function of the ACE1-AT1 R vasoconstrictor axis of the RAS system in mesenteric arteries from SHR, thereby improving the symptoms of hypertension.
作者
徐召霞
张慧荣
李丽
石丽君
XU Zhao-Xia;ZHANG Hui-Rong;LI Li;SHI Li-Jun(Department of Exercise Physiology,Beijing Sport University,Beijing 100084,China;Key Laboratory of Sports and Physical Health Ministry of Education,Beijing Sport University,Beijing 100084,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2020年第7期785-794,共10页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金资助项目(No.31771312)
中央高校基本科研业务费专项资金(No.2020GJ)资助。
