Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hepatol Res. 2009 Mar;39(3):247-55. doi: 10.1111/j.1872-034X.2008.00453.x. Epub 2008 Nov 20.
To investigate the choleretic effects of inchinkoto (ICKT) on livers of patients with biliary obstruction due to bile duct carcinoma.
Twenty-seven patients with bile duct carcinoma who were due to undergo biliary drainage and subsequent major hepatectomy were randomly assigned to preoperative ICKT (n = 13) or untreated (n = 14) groups. ICKT was administered from the day of admission until one day before surgery. Changes in bile constituents, expression of multidrug resistance-associated protein (MRP) 2, MRP3 and MRP4 in the liver, and the incidence of postoperative complications were included as end-points.
The biliary concentration of total bilirubin was significantly increased after administration of ICKT (23.7 +/- 2.8 mg/dL before ICKT; 34.0 +/- 4.0 mg/dL after ICKT, P < 0.05). The biliary concentration of total bile acids was also significantly increased. Protein levels of MRP2 and MRP3 in the crude plasma membrane fraction of livers of treated patients were significantly higher than those without treatment. MRP2 staining in the livers of patients without ICKT treatment was weak and diffuse around the bile canaliculi, whereas staining in patients with ICKT treatment was strong and restricted to the bile canaliculi.
ICKT exerts a choleretic effect on the livers of patients with biliary obstruction. This beneficial effect was associated with increased expression of MRP2. ICKT thus has therapeutic potential for treatment for obstructive cholestasis due to bile duct carcinoma.
研究胆硷能 Inchinkoto(ICKT)对胆管癌所致胆道梗阻患者肝脏的利胆作用。
27 例拟行胆道引流和随后行肝大部切除术的胆管癌患者被随机分为术前 ICKT(n=13)或未治疗(n=14)组。ICKT 从入院当天开始给药,直至手术前一天。将胆汁成分的变化、肝脏多药耐药相关蛋白(MRP)2、MRP3 和 MRP4 的表达以及术后并发症的发生率作为终点。
给药后胆汁总胆红素浓度明显升高(给药前 ICKT 为 23.7+/-2.8mg/dL;给药后 ICKT 为 34.0+/-4.0mg/dL,P<0.05)。胆汁总胆汁酸浓度也明显升高。经 ICKT 治疗患者肝脏粗质膜部分的 MRP2 和 MRP3 蛋白水平明显高于未治疗患者。未接受 ICKT 治疗的患者肝脏 MRP2 染色较弱且弥漫分布于胆小管周围,而接受 ICKT 治疗的患者染色较强且局限于胆小管。
ICKT 对胆管梗阻患者的肝脏具有利胆作用。这种有益作用与 MRP2 表达增加有关。因此,ICKT 对治疗胆管癌引起的梗阻性胆汁淤积具有治疗潜力。