Hepatic expression of multidrug resistance protein 2 in biliary atresia.
Hepatic expression of multidrug resistance protein 2 in biliary atresia.
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DOI：
10.1186/1476-5926-10-6
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发表时间：
2011-08-03
期刊：
影响因子：
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通讯作者：
Yoshida, Hideo
中科院分区：
文献类型：
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作者：
Terui, Keita;Saito, Takeshi;Yoshida, Hideo
背景：胆道闭锁（BA）是一种新生儿特发性炎性闭塞性胆管病，可导致进行性胆汁性肝硬化。肝门肠吻合术（加塞手术）可以治愈30%至80%的患者的黄疸。术后黄疸的清除是影响BA患者长期预后的重要因素之一。多药耐药蛋白2（MRP 2）是位于肝细胞中的小管输出泵之一;它输出有机阴离子及其缀合物（例如，胆红素）进入胆小管。虽然MRP 2是胆红素排泄的重要转运蛋白，但其在BA患者临床过程中的作用尚不清楚。本研究探讨肝MRP 2表达与BA患者的临床进程之间的关系，特别强调在治疗黄疸后hepatoportoenterostomy.Results：肝MRP 2表达水平之间没有显着差异观察BA和对照组。在BA组和对照组中，MRP 2表达与手术时的年龄无相关性。在BA患者中，黄疸组和无黄疸组的MRP 2表达水平无显著差异（2.0 * 10-4 vs 3.1 * 10-4，p = 0.094）。术前血清总胆红素水平与MRP 2表达水平无相关性（rs = 0.031，p = 0.914），2周时测定的血清总胆红素水平（rs =-0.569，p = 0.034）和术后4周（rs =-0.620，p = 0.018）与MRP 2表达水平显著相关。此外，MRP 2表达水平与4周内血清总胆红素水平变化的比率呈负相关（rs =-0.676，p = 0.008），该比率代表术后4周测量的血清胆红素水平除以术前值。MRP 2的表达水平与核受体，如维甲酸 * 受体α，法尼酯 * 受体，胆甾烷 * 受体，或组成androstane receptor.CONCLUSIONS：肝MRP 2的表达水平与BA患者术后黄疸的清除，至少在肝门肠吻合术后1个月内。这一发现表明，不仅肝组织的形态外观，而且肝细胞的生物学状态是重要的BA的病理生理。
BACKGROUND: Biliary atresia (BA) is an idiopathic inflammatory obliterative cholangiopathy of neonates, leading to progressive biliary cirrhosis. Hepatoportoenterostomy (Kasai procedure) can cure jaundice in 30% to 80% of patients. Postoperative clearance of jaundice is one of the most important factors influencing long-term outcomes of BA patients. Multidrug resistance protein 2 (MRP2) is one of the canalicular export pumps located in hepatocytes; it exports organic anions and their conjugates (e.g., bilirubin) into bile canaliculus. Although MRP2 is an essential transporter for the excretion of bilirubin, its role in the clinical course of BA patients is unclear. The present study investigated the relationship between hepatic MRP2 expression and clinical course in BA patients, with particular emphasis in curing jaundice after hepatoportoenterostomy.RESULTS: No significant differences in hepatic MRP2 expression level were observed between BA and controls groups. There was no correlation between MRP2 expression and age at time of surgery in BA and control groups. In BA patients, MRP2 expression level in the jaundice and jaundice-free group did not differ significantly (2.0 * 10-4 vs 3.1 * 10-4, p = 0.094). Although the serum level of total bilirubin just before surgery did not correlate with MRP2 expression level (rs = 0.031, p = 0.914), the serum level of total bilirubin measured at 2 weeks (rs = -0.569, p = 0.034) and 4 weeks after surgery (rs = -0.620, p = 0.018) were significantly correlated with MRP2 expression level. Furthermore, MRP2 expression level was inversely correlated with ratio of change in serum total bilirubin level over 4 weeks (rs = -0.676, p = 0.008), which represents the serum bilirubin level measured at 4 weeks after surgery divided by value just before surgery. There was no correlation between expression level of MRP2 and nuclear receptors, such as retinoid * receptor alpha, farnesoid * receptor, pregnane * receptor, or constitutive androstane receptor.CONCLUSIONS: Hepatic MRP2 expression level was associated with postoperative clearance of jaundice in BA patients, at least within 1 month after hepatoportoenterostomy. This finding suggests that not only morphological appearance of the liver tissue but also the biological status of hepatocytes is important for BA pathophysiology.