Splenic hemodynamics and decreased endothelial nitric oxide synthase in the spleen of rats with liver cirrhosis.
Splenic hemodynamics and decreased endothelial nitric oxide synthase in the spleen of rats with liver cirrhosis.
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DOI：
10.1016/j.lfs.2007.03.009
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发表时间：
2007-05
期刊：
影响因子：
6.1
通讯作者：
S. Yamaguchi;H. Kawanaka;D. Yoshida;Y. Maehara;M. Hashizume
中科院分区：
文献类型：
--
作者：
S. Yamaguchi;H. Kawanaka;D. Yoshida;Y. Maehara;M. Hashizume
肝硬化脾肿大被认为在门静脉高压症的发病机制中起作用，但脾血流动力学和分子机制尚未阐明。本研究旨在研究与脾脏微循环和充血相关的脾脏血流动力学，并确定在肝硬化大鼠脾脏内皮型一氧化氮合酶（eNOS）信号通路的状态。采用胆管结扎法建立肝硬化模型。在胆管结扎大鼠（BDL大鼠）和对照组大鼠中，使用激光多普勒流量计测量脾血流量，并使用近红外分光光度计测量脾血容量。同时检测脾脏eNOS及其上游效应因子Akt、TNF-α和VEGF的表达。与对照组相比，BDL大鼠的脾比血流量显著降低。BDL大鼠脾比血容量减少，而脾总血容量，尤其是去氧脾血容量显著增加。BDL大鼠脾脏中磷酸化eNOS和总eNOS的表达以及eNOS磷酸化率均显著降低。BDL大鼠脾脏中Akt磷酸化率和TNF-α浓度降低，VEGF表达增加。这些结果表明，eNOS信号通路被抑制在脾脏的硬化大鼠，并可能有助于测量的特定的血流量和体积的减少，在脾脏的肝硬化。确定影响eNOS在脾脏中抑制的因素可能有助于阐明肝硬化如何导致脾内循环动力低下。
The enlarged spleen in liver cirrhosis is considered to play a role in the pathogenesis of portal hypertension, but the splenic hemodynamics and molecular mechanisms behind the phenomenon have not been elucidated. The present study aimed to examine the splenic hemodynamics associated with splenic microcirculation and congestion, and to determine the status of the endothelial nitric oxide synthase (eNOS) signaling pathway in the spleen of rats with liver cirrhosis. Liver cirrhosis was induced by bile duct ligation. In rats with bile duct ligation (BDL rats) and control rats, splenic blood flow was measured using a laser Doppler flowmeter, and splenic blood volume was measured using a near-infrared spectrophotometer. The expressions of eNOS and its upstream effectors, Akt, TNF-α and VEGF, in the spleen were also determined. Specific splenic blood flow was significantly decreased in BDL rats compared with control rats. Specific splenic blood volume was also decreased in BDL rats, while their total splenic blood volume, especially the deoxygenated volume, was significantly increased. The expressions of phosphorylated and total eNOS, and the eNOS phosphorylation ratio, were all significantly decreased in the spleen of BDL rats. The Akt phosphorylation ratio and TNF-α concentration were also decreased in the spleen of BDL rats although the expression of VEGF was increased. These findings suggest that the eNOS signaling pathway is suppressed in the spleen of cirrhotic rats, and may contribute to the measured decreases in specific blood flow and volume in the spleen of liver cirrhosis. Determination of the factors influencing the suppression of eNOS in the spleen may shed light on how liver cirrhosis results in hypodynamic intrasplenic circulation.