背景:门脉高压症(PHT)的高动力循环取决于中枢神经激活。然而,向中枢神经心血管调节中枢发出PHT信号的启动机制尚不清楚.我们旨在检验以下假设:肠道中的氧化应激会启动激活门脉高压大鼠中央心血管核的信号。
方法:两组大鼠。一个人因部分门静脉结扎而产生门脉高压,而对照组进行了假手术。血流动力学包括门静脉压力,心输出量,测量平均动脉压(MAP)和外周血管阻力.通过下丘脑室旁核(PVN)中的免疫组织化学Fos表达来确定中央心血管核的激活。髓过氧化物酶活性,氧化应激标志物,在空肠中测量。过氧化氢,抗氧化剂N-乙酰半胱氨酸(NAC)或盐水对照通过灌胃或置于腹膜腔的渗透微型泵给药12-14天.
结果:与对照组相比,PHT大鼠心输出量增加(54.2±9.5vs33.6±2.4ml/min/100g体重,p<0.01),降低MAP(96.2±6.4mmHgvs103.2±7.8,p<0.01)和全身血管阻力(1.84±0.28vs3.14±0.19mmHg/min/ml/100gBW,p<0.01)。PHT大鼠空肠髓过氧化物酶和PVNFos表达增加。NAC治疗消除了高动力循环,PHT大鼠空肠髓过氧化物酶和PVNFos表达降低,但对假对照没有影响。H2O2显著增加PVNFos表达,降低MAP。
结论:这些结果表明,在PHT中,肠系膜氧化应激是激活化学感受器并通过中枢神经心血管调节中心触发高动力循环的初始信号。
BACKGROUND: Hyperdynamic circulation in portal hypertension (PHT) depends on central neural activation. However, the initiating mechanism that signals PHT to the central neural cardiovascular-regulatory centers remains unclear. We aimed to test the hypothesis that oxidative stress in the gut initiates the signal that activates central cardiovascular nuclei in portal hypertensive rats.
METHODS: Two groups of rats were used. One had portal hypertension produced by partial portal vein ligation, while controls underwent sham operation. Hemodynamics including portal pressure, cardiac output, mean arterial pressure (MAP) and peripheral vascular resistance were measured. Activation of central cardiovascular nuclei was determined by immunohistochemical Fos expression in the paraventricular nucleus (PVN) of the hypothalamus. Myeloperoxidase activity, an oxidative stress marker, was measured in the jejunum. Hydrogen peroxide, the antioxidant N-acetyl-cysteine (NAC) or saline controls were administered for 12-14 days by gavage or osmotic minipumps placed in the peritoneal cavity.
RESULTS: Compared with controls, PHT rats showed increased cardiac output (54.2 ± 9.5 vs 33.6 ± 2.4 ml/min/100 g BW, p < 0.01), decreased MAP (96.2 ± 6.4 mmHg vs 103.2 ± 7.8, p < 0.01) and systemic vascular resistance (1.84 ± 0.28 vs 3.14 ± 0.19 mmHg/min/ml/100 g BW, p < 0.01). PHT rats had increased jejunal myeloperoxidase and PVN Fos expression. NAC treatment eliminated the hyperdynamic circulation, decreased jejunal myeloperoxidase and PVN Fos expression in PHT rats, but had no effect on sham controls. H2O2 significantly increased PVN Fos expression and decreased MAP.
CONCLUSIONS: These results indicate that in PHT, mesenteric oxidative stress is the initial signal that activates chemoreceptors and triggers hyperdynamic circulation by central neural cardiovascular-regulatory centers.