大鼠肾交感神经与氧化应激在足底电击引发的高血压中的作用

Role of renal sympathetic nerve and oxidative stress in foot shock-induced hypertension in rats

为了探讨大鼠肾交感神经与氧化应激在慢性足底电击诱导的高血压中的作用，本研究将90只Sprague-Dawley大鼠随机平均分为6组：对照组、电击组、去肾交感神经组、去肾交感神经＋电击组、Tempol＋电击组、去肾交感神经＋Tempol＋电击组，对大鼠进行周期为14天的慢性足底电击，每天上、下午各给予一次足底电刺激，每次2 h，电流强度为2~4 mA，电压输出为75 V，脉冲间隔5~30 s，波宽50~100 ms。行肾交感神经去除术以去除大鼠双侧肾交感神经（术后休养一周）。抗氧化剂Tempol于每日电击前1 h腹腔注射。于电击第0、3、7、10、14天测量大鼠的血压，14天后经腹主动脉取血并经离心以收集血浆，测定血浆中的各项氧化应激指标、肾素和血管紧张素II浓度。结果显示：与对照组相比，电击组大鼠血压从第7天开始出现显著性升高，去肾交感神经及Tempol处理均抑制了电击引起的血压升高。在氧化应激指标中，电击组大鼠血浆中的硫代巴比妥酸反应物（thiobarbituric acid reactive substance, TBARS）水平显著高于对照组，而去肾交感神经＋电击组及Tempol＋电击组与电击组相比均有显著性降低；电击组、去肾交感神经＋电击组及Tempol＋电击组血浆中的谷胱甘肽过氧化物酶（gluta-thione peroxidase, GSH-Px）浓度显著低于对照组；电击组大鼠血浆中的肾素和血管经张素II浓度显著高于对照组，而去肾交感神经及Tempol处理后肾素和血管经张素II浓度均显著低于电击组。以上结果提示：肾交感神经在慢性足底电击诱导的高血压的发生过程中起着重要作用；肾交感神经可直接或间接影响肾素-血管紧张素-醛固酮系统（renin-angiotensin-aldosterone sys-tem, RAAS）的活动和氧化应激反应，从而使大鼠血压长期保持在高水平状态，最终形成高血压。

The present study was aimed to investigate the roles of renal sympathetic nerve and oxidative stress in the development of foot shock-induced hypertension. Ninety rats were divided into 6 groups（the number of each group was 15）： control group, foot shock group, denervation of renal sympathetic nerve group, denervation of renal sympathetic nerve ＋ foot shock group, Tempol treatment ＋ foot shock group, denervation of renal sympathetic nerve ＋ Tempol treatment ＋ foot shock group. Rats were received electrical foot shock for 14 days（2–4 m A, 75 V, shocks of 50–100 ms every 30 s, for 4 h each session through an electrified grid floor every day）. Renal sympathetic ablation was used to remove bilateral renal sympathetic nerve in rats（rats were allowed to recover for one week before the beginning of the foot shock procedure）. The antioxidant Tempol was injected intraperitoneally at 1 h before foot shock. Systolic blood pressure was measured at 1 h after foot shock on day 0, 3, 7, 10 and 14. Contents of thiobarbituric acid reactive substance（TBARS）, renin, angiotensin Ⅱ（AngⅡ） and glutathione peroxidase（GSH-Px） in plasma were measured by ELISA after 14-day foot shock. The results showed that systolic blood pressure of foot shock group was significantly increased（P 0.05） compared with that of control group from day 7 to day 14 of foot shock. Denervation of renal sympathetic nerve and/or Tempol treatment significantly reduced the increase of systolic blood pressure induced by foot shock. Levels of TBARS, renin and Ang II in plasma were increased significantly in foot shock group compared with that of control group（P 0.05）. Plasma GSH-Px concentration was decreased in foot shock group rats compared with that of control group（P 0.05）. Denervation of renal sympathetic nerve and/or tempol treatment significantly reduced the increase in TBARS, renin, Ang Ⅱ levels induced by foot shock in comparison with that of foot shock group（P 0.05）, but had no effects on the reduction of GSH-Px concentration. The results suggest that renal sympathetic nerve may play an important role in the development of foot shock-induced hypertension, and renal sympathetic nerve may influence oxidative stress and directly or indirectly activate renin-angiotensin-aldosterone system, so the foot shock-induced high blood pressure may be maintained and hypertension may therefore be produced.