Suto Koichi, Fuse Akira, Igarashi Yukio, Kimura Wataru
First Department of Surgery, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
J Surg Res. 2002 Jul;106(1):62-9. doi: 10.1006/jsre.2002.6437.
Hyperbilirubinemia occurs as a sign of hepatic failure after hepatectomy. The pathogenesis of this event has not been elucidated. In cases complicated with postoperative infection, hyperbilirubinemia is prolonged and the composition of bilirubin subfractions in bile changes markedly. A reduction in the proportion of bilirubin diglucuronide (BDG) is especially notable. This study was aimed at clarifying the relationship between infection and biliary bilirubin subfractions, with a view to shedding light on the mechanisms of change.
Rats underwent either laparotomy or partial hepatectomy (Hx). Daily intraperitoneal injections of lipopolysaccharide (LPS) or natural saline were administered for 3 days following surgery. Total serum bilirubin levels and proportions of BDG and bilirubin in bile were measured until Day 5 after the operation. Hepatic levels of UDP-glucuronic acid (UDP-GA), UDP-glucose, NAD(+), and total adenine nucleotides (TAN) and activities of UDP-glucuronyltransferase (UDP-GT) and UDP-glucose dehydrogenase were measured on Day 4.
In hepatectomized rats treated with LPS (Hx-LPS), total serum bilirubin levels were elevated, biliary bilirubin levels were decreased, and the proportion of biliary BDG was decreased on Day 4. Hepatic levels of UDP-GA, NAD(+), and TAN and activities of UDP-GT in Hx-LPS were reduced. In all groups tested, a significant linear correlation between BDG and UDP-GA and between UDP-GA and NAD(+) was found.
The reduction of UDP-GA might be effected by reduced hepatic levels of NAD(+) in endotoxemia following hepatectomy. It is therefore suggested that alterations in biliary bilirubin subfractions might accurately reflect the energy state of the remnant liver following hepatectomy.
高胆红素血症是肝切除术后肝衰竭的一种表现。这一现象的发病机制尚未阐明。在合并术后感染的病例中,高胆红素血症会持续更长时间,胆汁中胆红素亚组分的构成会发生显著变化。尤其值得注意的是双葡萄糖醛酸胆红素(BDG)比例的降低。本研究旨在阐明感染与胆汁胆红素亚组分之间的关系,以期揭示变化机制。
对大鼠进行剖腹手术或部分肝切除术(Hx)。术后3天每天腹腔注射脂多糖(LPS)或生理盐水。在术后第5天前测量血清总胆红素水平以及胆汁中BDG和胆红素的比例。在第4天测量肝脏中尿苷二磷酸葡萄糖醛酸(UDP-GA)、尿苷二磷酸葡萄糖、烟酰胺腺嘌呤二核苷酸(NAD(+))、总腺嘌呤核苷酸(TAN)的水平以及尿苷二磷酸葡萄糖醛酸转移酶(UDP-GT)和尿苷二磷酸葡萄糖脱氢酶的活性。
在接受LPS治疗的肝切除大鼠(Hx-LPS)中,术后第4天血清总胆红素水平升高,胆汁胆红素水平降低,胆汁中BDG的比例降低。Hx-LPS组肝脏中UDP-GA、NAD(+)和TAN的水平以及UDP-GT的活性降低。在所有测试组中,发现BDG与UDP-GA之间以及UDP-GA与NAD(+)之间存在显著的线性相关性。
肝切除术后内毒素血症中,肝脏NAD(+)水平降低可能会导致UDP-GA减少。因此,提示胆汁胆红素亚组分的改变可能准确反映肝切除术后残余肝脏的能量状态。