Department of Gastroenterology, Turkiye Yuksek İhtisas Education and Research Hospital, Sihhiye, 06100 Ankara, Turkey.
Clin Res Hepatol Gastroenterol. 2011 Oct;35(10):644-9. doi: 10.1016/j.clinre.2011.06.008. Epub 2011 Jul 29.
Cholangiocarcinoma (CCA) is a primary neoplastic tumor of the epithelial lining of the biliary tree which carries a poor prognosis despite combined therapeutic strategies. Although the exact etiology remains obscure, it has been suggested that locally produced Angiotensin II (Ang II) in intrahepatic CCA tissues plays a key role in the proliferation and activation of CCA. In the present study, we aimed to analyze the relationship between the levels of circulating angiotensin converting enzyme (ACE), an important molecule of the renin-angiotensin system (RAS), and biliary disorders.
The study group comprised 19 extrahepatic cholangiocarcinoma (EHCC) (16 patients with hilar, three patients with distal CCA), and 15 choledocolithiasis (CL) patients, with 15 controls. Median age of EHCC, CL and healthy controls were 67 (48-82), 65 (29-87) and 56 (23-74) respectively. ACE was measured by monitoring the alteration in absorbance at 340 nm of the hydrolysis of furylacrylolylphenylalanylglycylglycine (FAPGG) to FAP and GG on an analyzer. The ACE activity in the sample was determined by comparing the sample reaction rate to that obtained with the ACE calibrator.
Serum mean ACE levels were 56.6±27.4 U/L, 32.9±14.6 U/L and 28.6±10.6 U/L for patients with EHCC, CL and healthy controls, respectively. Serum ACE levels were significantly higher in patients with EHCC compared to CL and control groups. No significant differences with respect to ACE levels were observed between CL and control groups.
Circulating ACE in the context of RAS might be associated with EHCC development by creating a local environment enriched with cytokines and other growth factors that may promote cholangiocyte turnover.
胆管癌（CCA）是一种原发性上皮性胆道肿瘤，尽管采用了联合治疗策略，但预后仍然很差。尽管确切的病因尚不清楚，但有人认为肝内 CCA 组织中局部产生的血管紧张素 II（Ang II）在 CCA 的增殖和激活中起关键作用。在本研究中，我们旨在分析循环血管紧张素转换酶（ACE）水平与胆道疾病之间的关系，ACE 是肾素-血管紧张素系统（RAS）的重要分子。
研究组包括 19 例肝外胆管癌（EHCC）（16 例肝门部，3 例远端 CCA）和 15 例胆石症（CL）患者，对照组为 15 例。EHCC、CL 和健康对照组的中位年龄分别为 67（48-82）、65（29-87）和 56（23-74）。ACE 通过监测 furylacrylolylphenylalanylglycylglycine（FAPGG）水解为 FAP 和 GG 时 340nm 处吸光度的变化，在分析仪上监测 ACE 的变化。通过比较样品反应速率与 ACE 校准品的反应速率，确定样品中的 ACE 活性。
EHCC、CL 和健康对照组患者的血清平均 ACE 水平分别为 56.6±27.4U/L、32.9±14.6U/L 和 28.6±10.6U/L。EHCC 患者的血清 ACE 水平明显高于 CL 组和对照组。CL 组和对照组 ACE 水平无显著差异。
RAS 中循环 ACE 可能通过创造富含细胞因子和其他生长因子的局部环境来促进胆管细胞的更替，从而与 EHCC 的发生有关。
