Urotensin II modulates hepatic fibrosis and portal hemodynamic alterations in rats.
Urotensin II modulates hepatic fibrosis and portal hemodynamic alterations in rats.
复制标题
尾加压素 II 调节大鼠肝纤维化和门静脉血流动力学改变。
DOI：
10.1152/ajpgi.00127.2009
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
H. Krum
中科院分区：
文献类型：
--
作者：
W. Kemp;A. Kompa;A. Phrommintikul;C. Herath;J. Zhiyuan;P. Angus;C. Mclean;S. Roberts;H. Krum
循环中的尾加压素 II (UII) 对肝脏疾病和门静脉高压的影响尚不清楚。我们的目的是评估 UII 是否在肝纤维化和门静脉高压的发展中发挥致病作用。将20只健康大鼠连续输注4周以上，分为三个治疗组：对照组（生理盐水，n = 7）、低剂量组（UII，1 nmol x kg(-1) x h(-1)，n = 8）和高剂量组（UII，3 nmol x kg(-1) x h(-1)，n = 5）。评估了纤维化的血流动力学参数和形态定量，并测定了肝组织中的促纤维化细胞因子和纤维化标志物。 UII 引起门静脉压显着的剂量依赖性增加（分别为 5.8 +/- 0.4、6.4 +/- 0.3 和 7.6 +/- 0.7，P = 0.03）。高剂量UII输注与转化生长因子-β（P < 0.05）和血小板衍生生长因子-β（P = 0.06）的肝转录物增加相关。高剂量组肝组织羟脯氨酸升高（P < 0.05）。没有发现全身血流动力学改变。我们得出结论，UII 输注会升高正常大鼠的门静脉压力并诱导肝纤维化。这种反应可能是通过诱导纤维形成细胞因子介导的。这些发现对人类肝脏疾病具有病理生理学意义，在人类肝脏疾病中观察到血浆 UII 水平升高。
The influence of circulating urotensin II (UII) on liver disease and portal hypertension is unknown. We aimed to evaluate whether UII executes a pathogenetic role in the development of hepatic fibrosis and portal hypertension. UII was administered by continuous infusion over 4 wk in 20 healthy rats divided into three treatment groups, controls (saline, n = 7), low dose (UII, 1 nmol x kg(-1) x h(-1), n = 8), and high dose (UII, 3 nmol x kg(-1) x h(-1), n = 5). Hemodynamic parameters and morphometric quantification of fibrosis were assessed, and profibrotic cytokines and fibrosis markers were assayed in hepatic tissue. UII induced a significant dose-dependent increase in portal venous pressure (5.8 +/- 0.4, 6.4 +/- 0.3, and 7.6 +/- 0.7, respectively, P = 0.03). High-dose UII infusion was associated with an increase in hepatic transcript for transforming growth factor-beta (P < 0.05) and platelet-derived growth factor-beta (P = 0.06). Liver tissue hydroxyproline was elevated in the high-dose group (P < 0.05). No systemic hemodynamic alterations were noted. We concluded that UII infusion elevates portal pressure and induces hepatic fibrosis in normal rats. This response may be mediated via induction of fibrogenic cytokines. These findings have pathophysiological implications in human liver disease where increased plasma UII levels have been observed.
影响因子：
8.3
作者：
Watanabe, T;Suguro, T;Miyazaki, A
通讯作者：
Miyazaki, A