Chan Cho-Yu, Lee Fa-Yauh, Wang Teh-Fang, Huang Seng-Wong, Chang Full-Young, Lu Rei-Hwa, Chen Yi-Chou, Wang Sun-Sang, Huang Hui-Chun, Lee Shou-Dong
Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan.
J Gastroenterol Hepatol. 2006 Sep;21(9):1483-7. doi: 10.1111/j.1440-1746.2006.04261.x.
The pathogenetic mechanisms of hepatic encephalopathy (HE) are not fully understood. Cerebral blood flow regulated by cyclooxygenase (COX) may be involved in the development of HE. There are no comprehensive data concerning the effects of COX 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). Those rats were then divided into two groups to receive i.p. injection of indomethacin (5 mg/kg per day) or distilled water for 7 days from day 36 to day 42 after BDL. The control group consisted of rats receiving a sham operation. Severity of encephalopathy was assessed by counts of motor activity. Plasma levels of tumor necrosis factor (TNF)-alpha and 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), and liver biochemistry tests were determined after treatment.
The motor activity in both groups of BDL rats were significantly lower than that of the control group (P < 0.001). As compared with the BDL rats treated with distilled water, BDL rats treated with indomethacin had significant lower levels of 6-keto-PGF(1alpha), but the motor activity, TNF-alpha levels and serum biochemistry tests were not significantly different between both BDL groups.
Chronic indomethacin 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。由环氧化酶（COX）调节的脑血流量可能参与了HE的发生发展。目前尚无关于COX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。然后将这些大鼠分为两组，从BDL术后第36天至第42天，腹腔注射吲哚美辛（每天5 mg/kg）或蒸馏水，持续7天。对照组为接受假手术的大鼠。通过运动活动计数评估脑病的严重程度。治疗后测定血浆肿瘤坏死因子（TNF）-α和6-酮-前列腺素F（1α）（6-keto-PGF（1α））水平以及肝脏生化指标。
两组BDL大鼠的运动活动均显著低于对照组（P < 0.001）。与用蒸馏水治疗的BDL大鼠相比，用吲哚美辛治疗的BDL大鼠6-keto-PGF（1α）水平显著降低，但两组BDL大鼠的运动活动、TNF-α水平和血清生化指标无显著差异。
长期给予吲哚美辛对BDL大鼠脑病的严重程度没有显著的有害或治疗作用。
