自发性高血压大鼠不同G蛋白信号调节因子的变化

Changes of different regulators of G protein signaling in spontaneously hypertensive rat

目的通过检测自发性高血压大鼠(spontaneously hypertensive rats,SHR)不同组织G蛋白信号调节因子(regulator of G protein signaling,RGS)包括RGS2、RGS3和RGS4 mRNA的变化及其与心血管系统生理学表型的相关性,探讨其在高血压中的作用及机制。方法SHR与正常血压对照组Wistar大鼠经颈动脉插管测量血流动力学指标,同时测定心重指数(heart weight/body mass,HW/BM)和左室质量指数(left ventricular mass index,LVMI)。提取主动脉和心肌组织总RNA,逆转录后采用实时定量聚合酶链式反应方法检测RGS2、RGS3和RGS4 mRNA水平。结果SHR组收缩压(229.2±30.6mm Hg比121.2±12.8mm Hg,P<0.01),HW/BM(0.34±0.01比0.26±0.01,P<0.01)和LVMI(0.28±0.01比0.21±0.01,P<0.01)均显著高于对照组。SHR组RGS2 mRNA水平与对照组相比,在主动脉中降低41.5%(0.69±0.14比1.18±0.26,P<0.05),心肌中升高3.3倍(0.20±0.04比0.06±0.01,P<0.05);SHR组主动脉和心肌中RGS3 mRNA水平分别较对照组升高4.2倍(1.51±0.20比0.36±0.06,P<0.01)和4.6倍(3.16±0.36比0.68±0.09,P<0.05)。SHR与对照组主动脉和心肌RGS4 mRNA水平差异无统计学意义。大鼠主动脉RGS2 mRNA水平与收缩压呈负相关(Y=-0.003X+0.89,P<0.05);心肌RGS2 mRNA水平与HW/BM(Y=1.56X-0.35,P<0.05)呈正相关。大鼠主动脉和心肌组织RGS3 mRNA水平呈正相关(P<0.05),并分别与收缩压(Y=0.01X-0.65,P<0.05)和LVM I(Y=23.8X-4.2,P<0.05)呈正相关。结论SHR大鼠主动脉选择性RGS2降低和RGS3升高可能参与了SHR高血压的发病,心脏RGS2和RGS3 mRNA水平升高与心肌肥厚和心脏收缩功能改变相关,提示RGS2和RGS3可能成为高血压及其心脏并发症药物治疗的新靶点。

Objective To study changes of different regulators of G protein signaling （RGS） including RGS2, RGS3 and RGS4 mRNA in aorta and heart of spontaneously hypertensive rats （SHR）, as well as their correlation with physiological phenotype of cardiovascular system. Methods Haemodynamic indexes of the cardiovascular system were measured. Heart weight and left ventricular weight were determined to calculate the ratio of heart weight to body mass （ HW/BM ） as well as left ventricular mass index （ LVMI ） in both male SHR and Wistar rats. Real-time PCR after RT were performed to determine the level of RGS mRNA in aorta and heart. Results Systolic blood pressure （SBP） of SHR was significantly higher than that of the control （229 ± 29 vs. 121 ± 12 mm Hg, P 〈 0. 01 ）, as well as HW/BM （0. 34 ± 0.01 vs. 0.26 ± 0.01, P〈0.01） andLVMI （0.28 ± 0.01 vs. 0.21 ± 0.01, P〈0.01）. Comparing with the control, RGS2 mRNA in the aorta of SHR decreased 41.5% （0.69 ± 0.14 vs. 1.18 ±0.26, P〈 0. 05）, but increased in heart tissue by about 3.3 times（0. 20 ± 0. 04 vs. O. 06 ± 0. 01, P 〈0. 05）. RGS3 mRNA in both the aorta and heart tissue were significantly increased by 4. 2 （ 1.51 ± 0. 20 vs. O. 36 ± 0. 06, P〈0.01）and4.6 times （3.16±0.36 vs. 0.68 ±0.09, P〈0.05）, respectively; RGS4 mRNA in the aorta and the heart of SHR had no significant difference comparing with the control. RGS2 mRNA in the aorta was negatively correlated with SBP （ P 〈 0. 05 ）, but heart RGS2 mRNA was positively correlated with HW/BM （P 〈 0. 05 ）. RGS3 mRNA in aorta and heart were positively correlated with SBP （P 〈 0. 05 ） and LVMI （ P 〈 0. 05 ）. Conchlsion Selective decrease of aorta RGS2 mRNA and increase of RGS3 mRNA in both aorta and heart of SHR may contribute to the pathogenesis of hypertension. RGS2 and RGS3 may be prospective new targets for treatment of hypertension.