室旁核中血管紧张素Ⅱ通过活性氧介导慢性间歇性低氧大鼠的升压作用

摘要

目的：研究室旁核( PVN)中血管紧张素Ⅱ( Ang Ⅱ)-活性氧(ROS)通路在慢性间歇性低氧(CIH)大鼠的升压作用。方法将雄性SD大鼠随机分为对照组和慢性间歇性低氧组(CIH 组)(8 h/d,连续15 d)。用立体定位仪进行PVN核团定位微量注射,采用颈动脉插管法在体测量大鼠平均动脉压(MAP),ELISA 法测量 PVN 中 Ang Ⅱ、ROS 含量, Western blot 法测定 PVN 中血管紧张素Ⅱ1型受体(AT1R)的蛋白表达,应用试剂盒(羟胺法)测定PVN中的总超氧化物歧化酶(T-SOD)活力。结果与对照组比较,CIH组大鼠PVN中ROS(P<0．05)和Ang Ⅱ含量显著升高(P<0．01),AT1R的表达显著增加(P<0．05),而T-SOD活力则明显下降( P <0．01)。双侧 PVN 内微量注射 Ang Ⅱ(0．3 nmol)可升高两组大鼠的MAP,而CIH大鼠MAP升高更显著(P<0．01)；超氧阴离子清除剂Tempol可降低两组大鼠的MAP,而CIH大鼠MAP降低更显著(P<0．01)；Tempol预处理可抑制Ang Ⅱ对两组大鼠的升压作用,且在CIH组中抑制作用更加明显( P<0．01)。结论室旁核中ROS介导了Ang Ⅱ在CIH大鼠中的升压作用。%Objective To investigate the effect of Ang II-ROS signal pathway in the hypothalamic paraventricular nucleus ( PVN) on chronic intermittent hypoxia( CIH) induced-hypertension in rats. Methods Male SD rats were randomly divided into control and CIH groups. The control rats were exposed to continuous normoxia, while the CIH rats were submitted to CIH (8 h per day for 15 days) . Rats were fixed on the stereotaxic instrument to conduct microinjection in the PVN according to Paxinos and Watson rat atlas. Mean arterial pressure ( MAP) was recorded in vivo on a PowerLab data acquisition system. We used ELISA kit to measure the content of AngⅡ, ROS, total-superoxide dismutase (T-SOD) and Western blot to measure AngⅡtype 1 receptor (AT1R) protein expression in PVN. Results The contents of PVN ROS(P<0. 05)and AngⅡ(P<0. 01) were significantly higher than that in control rats, along with increased AT1R protein expression(P<0. 05). The activity of PVN T-SOD in CIH rats was significantly lower than that in control rats(P<0. 01). Microinjection of Ang Ⅱ(0. 3 nmol) in bilateral PVN in-creased MAP in both CIH and control rats, and this response was significantly augmented in CIH rats(P<0. 01). ROS scavenger Tempol caused significant MAP decreases in CIH rats than that in control group(P<0. 01). Tem-pol prevented Ang Ⅱ-induced increases in MAP in both CIH and control rats, and this response was significantly augmented in CIH rats(P<0. 01). Conclusion The results suggest that the ROS in PVN mediates the increased blood pressure induced by Ang Ⅱ in CIH induced-hypertension rats.