摘要
目的:研究心力衰竭时压力感受性反射功能减退与脑内活性氧簇升高的关系,探讨压力感受性反射功能衰减的细胞内信号分子。方法:在心肌梗死诱发心力衰竭(心衰)的模型中,静脉注射苯肾上腺素和硝普钠,以血压变化与肾交感神经活动反应的关系作为评价压力感受性反射功能的指标。侧脑室给药改变脑内活性氧簇(ROS)水平,观察心衰大鼠压力感受性反射功能的变化。检测下丘脑ROS水平和NADPH氧化酶表达,反映脑内ROS的水平和来源。结果:(1)与对照组比较,心衰组压力感受反射调节肾交感神经活动功能曲线的范围、平均斜率和最大增益分别为(92.2±9.9)mmHg、(0.07%±0.01%)/mmHg和(1.20%±0.10%)/mmHg,均明显低于对照组的(65.6±7.4)mmHg、(0.13%±0.02%)/mmHg和(3.00%±0.20%)/mmHg(P<0.01);而功能曲线的最低值则高于对照组[(21.6%±4.8%)vs(7.5%±2.1%),P<0.01]。(2)侧脑室灌流超氧阴离子捕获剂tempol和NADPH氧化酶抑制剂apocynin明显增强心衰大鼠压力感受反射功能,而给予超氧化物歧化酶抑制剂DETC(dieth-yldithiocarbamate)则抑制对照组压力感受反射功能。(3)心衰组下丘脑活性氧水平明显高于对照组[(73.9±9.8)RLU.5min-1.mg-1vs(40.6±7.1)RLU.5min-1.mg-1,P<0.01]。(4)心衰大鼠下丘脑室旁核NADPH氧化酶亚单位gp91蛋白表达比对照组增加了1.3倍。结论:下丘脑细胞内ROS升高是介导心衰时压力感受性反射功能衰减的重要机制,脑内ROS增加主要源于NADPH氧化酶表达增强。
AIM： To determine the effect of reactive oxygen species on the baroreflex and to investigate the intracellular mechanism responsible for baroreflex dysfunction in the heart failure state. METHODS ： In the rat model of cardiomyocytes infarct induced heart failure, baroreflex function was evaluated by measuring the relationship between renal sympathetic nerve activity（RSNA） responses and change of blood pressure by intravenous injection of nitroglycerin and phenylephrine. Alteration in baroreflex function was measured under the different reactive oxygen species（ROS） level induced by intracerebroventricular administration of several chemicals. RESULTS ： （ 1 ） The range of RSNA response, average slope and maximum gain of baroreflex function curve were （ 92. 2 ±9. 9 ） mmHg, （ 0. 07% ± 0.01% ）/mmHg and （ 1.20%±0. 10% ）/mmHg, respectively, in CHF rats, which were significantly lower than those in sham rats（65.6 ± 7.4） mmHg, （0. 13% ±0. 02% ）/mmHg and（3.00%±0. 20% ）/mmHg（ P 〈 0. 01 ）. The minimum RSNA of baroreflex curve was higher in CHF rats than that in sham rat [ （21.6% ±4. 8% ） vs （7.5% ±2. 1% ）, P 〈 0. 01 ]. （2） Intracerebroventricular （icy） infusion of superoxide scavenger tempol and NADPH oxidase inhibitor apocynin significantly improved the blunted baroreflex in CHF rats. On contrast, icy administration of superoxide dismutase inhibitor diethyldithiocarbamate（DETC） decreased baroreflex function in sham rats. （3）The superoxide production in the hypothalamus of CHF rats was higher than that in sham rats[ （73. 9 ±9. 8）RLU·5min^-1·mg^-1vs（40.6±7.1）RLU·5min^-1·mg^-1,P〈0.01].（4）Protein expression of NADPH oxidase subunits gp91 phox in the paraventricular nucleus of the hypothalamus were increased by 1.3 fold in CHF rats than that in sham rats. CONCLUSION： Elevated intracellular ROS in the hypothalarnus plays an important role in the attenuation of baroreflex function in the heart failure state and results from upregulation of NADPH oxidase protein expression.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2009年第5期833-838,共6页
Chinese Journal of Pathophysiology
基金
美国NIH研究资助项目(No.PO1-HL-62222)
福建医科大学博士基金资助项目(No.BS07002)
