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目的探讨早期氯沙坦干预对自发性高血压大鼠(SHR)成年后血压、心肌肥厚以及心肌中血管紧张素Ⅱ1型受体(AT1R)b亚型(AT1bR)和AT1R相关蛋白(ATRAP)基因启动子区甲基化的影响。方法将雄性SHR子鼠分为出生前、出生后、出生前后序贯氯沙坦干预组和非干预组。在8周龄和16周龄时,应用尾测法测定大鼠收缩压,称重并计算左心室质量(LVM)/体质量(BM),实时定量逆转录聚合酶链反应(RT-PCR)及Western-blot法测定左心室心肌AT1bR、ATRAP的mRNA及蛋白表达,重亚硫酸盐修饰PCR结合焦磷酸测序法测定AT1bR和ATRAP基因启动子区的甲基化水平。结果 16周龄时,3个氯沙坦干预组的SHR收缩压及LVM/BM较非干预组低[收缩压:出生前氯沙坦干预组(173.8±8.5),出生后氯沙坦干预组(145.4±9.7),出生前后序贯氯沙坦干预组(138.5±6.7)比非干预组(197.4±7.6)mm Hg;LVM/BM:出生前氯沙坦干预组(2.39±0.14),出生后氯沙坦干预组(2.00±0.11),出生前后序贯氯沙坦干预组(1.97±0.08)比非干预组(3.18±0.21)mg/g;均P<0.05]。与非干预组相比,3个氯沙坦干预组心肌中AT1bR mRNA和AT1R蛋白表达降低,ATRAP mRNA及蛋白表达升高,AT1bR基因启动子区的甲基化程度无改变,ATRAP基因启动子区的甲基化程度减少。结论早期氯沙坦干预能延缓SHR成年后血压的上升,改善心肌肥厚,减少心肌中ATRAP基因启动子区的甲基化。
Objective To investigate the effect of early losartan on blood pressure, cardiac hypertrophy and the expression of angiotensin Ⅱ type 1 receptor (AT1bR) and AT1R related protein (ATRAP) genes in spontaneously hypertensive rats (SHR) Effect of promoter methylation. Methods Male SHR offspring were divided into before birth, after birth, before and after birth, losartan intervention group and non-intervention group. At 8 weeks of age and 16 weeks of age, the systolic pressure of rats was measured by tail test, and the left ventricular mass (LVM) / body mass (BM), the real time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) The mRNA and protein expression of AT1bR and ATRAP in left ventricular myocardium were detected by Western blotting. The methylation levels of AT1bR and ATRAP gene promoters were determined by bisulfite modified PCR and pyrosequencing. Results At 16 weeks of age, SHR systolic pressure and LVM / BM in three losartan groups were lower than those in non-intervention group [systolic pressure: losartan before birth (173.8 ± 8.5), losartan after birth (145.4 ± 9.7), and those in losartan group before and after birth (138.5 ± 6.7 vs 197.4 ± 7.6 mmHg; LVM / BM: losartan before intervention group (2.39 ± 0.14) (2.00 ± 0.11) in the losartan group and 1.97 ± 0.08 in the sequential losartan group before and after birth (3.18 ± 0.21) mg / g, all P <0.05]. Compared with non-intervention group, the expression of AT1bR mRNA and AT1R protein, the expression of ATRAP mRNA and protein in myocardium of 3 losartan intervention groups were increased, and the methylation level of AT1bR gene promoter region was unchanged. The ATRAP gene promoter region Reduce the degree of methylation. Conclusion Early losartan can delay the increase of blood pressure after SHR, improve cardiac hypertrophy and reduce the methylation of ATRAP promoter in myocardium.