Chan C-Y, Huang S-W, Wang T-F, Lu R-H, Lee F-Y, Chang F-Y, Chu C-J, Chen Y-C, Chan C-C, Huang H-C, Lee S-D
Taipei Veterans General Hospital, Armed Forces Sungshan Hospital, and National Yang-Ming University School of Medicine, Taipei, Taiwan.
Eur J Clin Invest. 2004 Feb;34(2):122-8. doi: 10.1111/j.1365-2362.2004.01295.x.
The pathogenetic mechanisms of hepatic encephalopathy (HE) are not fully understood. Vasodilatation induced by nitric oxide (NO) may be involved in the development of HE. There is no comprehensive data concerning the effects of NO inhibition on HE in chronic liver disease.
Male Sprague-Dawley rats weighing 240-270 g at the time of surgery were selected for experiments. Secondary biliary cirrhosis was induced by bile duct ligation (BDL). Counts of movements were compared between BDL rats and rats receiving a sham operation. In another series of experiments, BDL rats received either Nomega-nitro-L-arginine methyl ester (L-NAME, 25 mg kg-1 day-1 in tap water) or tap water (control) from the 36th to 42nd days after BDL. Besides motor activities, plasma levels of tumour necrosis factor (TNF)-alpha and nitrate/nitrite, liver biochemistry tests and haemodynamics were determined after treatment.
Compared with the sham-operated rats, the total, ambulatory and vertical movements were significantly decreased in the BDL rats (P </= 0.001). The L-NAME group had a significantly higher mean arterial pressure than that of the control group (119.0 +/- 2.5 mmHg vs. 97.3 +/- 2.8 mmHg, P = 0.002). However, the counts of motor activities, plasma levels of TNF-alpha and nitrate/nitrite, and serum biochemistry tests were not significantly different between the L-NAME and control groups.
Bile duct ligation may induce HE evidenced by a decrease in motor activities. However, chronic L-NAME administration did not have significantly detrimental or therapeutic effects on the severity of encephalopathy in BDL rats.
肝性脑病（HE）的发病机制尚未完全明确。一氧化氮（NO）诱导的血管舒张可能参与了HE的发生发展。目前尚无关于NO抑制对慢性肝病中HE影响的全面数据。
选择手术时体重为240 - 270 g的雄性Sprague-Dawley大鼠进行实验。通过胆管结扎（BDL）诱导继发性胆汁性肝硬化。比较BDL大鼠与接受假手术大鼠的活动计数。在另一系列实验中，BDL大鼠在BDL后第36至42天接受Nω-硝基-L-精氨酸甲酯（L-NAME，自来水中25 mg·kg-1·天-1）或自来水（对照）。治疗后除了测定运动活性外，还测定了血浆肿瘤坏死因子（TNF）-α水平、硝酸盐/亚硝酸盐水平、肝脏生化指标及血流动力学。
与假手术大鼠相比，BDL大鼠的总活动、自主活动和垂直活动显著减少（P≤0.001）。L-NAME组的平均动脉压显著高于对照组（119.0±2.5 mmHg对97.3±2.8 mmHg，P = 0.002）。然而，L-NAME组与对照组之间的运动活性计数、血浆TNF-α水平、硝酸盐/亚硝酸盐水平及血清生化指标并无显著差异。
胆管结扎可通过运动活性降低诱导HE。然而，长期给予L-NAME对BDL大鼠肝性脑病的严重程度并无显著有害或治疗作用。
