非酒精性脂肪性肝炎在大鼠模型中诱导与内脏血管舒张和高动力循环相关的非纤维性相关门脉高压，无论是在体外还是体内。

Non-alcoholic steatohepatitis induces non-fibrosis-related portal hypertension associated with splanchnic vasodilation and signs of a hyperdynamic circulation in vitro and in vivo in a rat model.

机构信息

Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp, Belgium.

出版信息

Liver Int. 2010 Mar;30(3):365-75. doi: 10.1111/j.1478-3231.2009.02136.x. Epub 2009 Oct 13.

DOI:10.1111/j.1478-3231.2009.02136.x

PMID:19840249

Abstract

INTRODUCTION

Steatosis, without fibrosis, may lead to changes in liver blood flow, which are poorly understood, and to date have not been correlated to portal pressure and related haemodynamics.

AIMS

To study the temporal relation between progressive steatosis, portal pressure, systemic haemodynamics, vascular responsiveness, mesenteric and portal blood flow in methionine-choline-deficient diet (MCDD)-fed rats.

METHODS

Male Wistar rats fed the MCDD were examined at week (w) 0-1-2-3-4-5-6-7-8, respectively, including systemic haemodynamics and portal pressure. At w0-4-8, in vivo blood flow was measured in the portal vein and the superior mesenteric artery. Dose-response curves to phenylephrine (PE) were established in abdominal aortic rings.

RESULTS

Histology showed 100% steatosis from w3 on. Fibrosis was absent. Significant inflammation was nearly absent upon w4. Portal pressure slightly increased at w2, reached a maximum at w4 [9.4 +/- 0.3 vs 2.9 +/- 0.6 mmHg at w0 (P=0.003)] and remained stable upon w8. Mean arterial blood pressure (MABP) decreased from w2 on [98.7 +/- 5.7 mmHg on w4 compared with 123.8 +/- 1.8 on w0 (P=0.002)]. Portal flow increased from 1.85 +/- 0.11 to 3.07 +/- 0.44 ml/min/100 g on w0 and w8 respectively (P=0.039). Mesenteric artery flow increased from 3.40 +/- 0.26 to 4.56 +/- 0.30 ml/min/100 g on w0 and w8 respectively (P=0.043). Vascular responsiveness to PE gradually decreased from 138 +/- 3% on w0 to 110 +/- 5% on w4 (P=0.013).

CONCLUSION

Steatohepatitis induces significant portal hypertension (PHT) in the absence of fibrosis, associated with an increase in mesenteric arterial and portal venous flow, arterial hyporesponsiveness to vasoconstrictors and a decrease in MABP, indicating the presence of splanchnic vasodilation and hyperdynamic circulation. These alterations resemble those seen in cirrhotic PHT.

摘要

简介

无纤维化的脂肪变性可能导致肝血流发生变化，但其变化尚不清楚，且迄今为止尚未与门脉压及其相关血液动力学相关联。

目的

研究逐渐发生的脂肪变性、门脉压、全身血液动力学、血管反应性、肠系膜和门脉血流之间的时间关系，在蛋氨酸-胆碱缺乏饮食（MCDD）喂养的大鼠中。

方法

雄性 Wistar 大鼠分别在第 0-1-2-3-4-5-6-7-8 周时接受 MCDD 喂养，检测包括全身血液动力学和门脉压。在第 0-4-8 周时，在门静脉和肠系膜上动脉中测量活体血流。在腹主动脉环中建立对苯肾上腺素（PE）的剂量反应曲线。

结果

组织学显示从第 3 周开始出现 100%的脂肪变性。无纤维化。第 4 周时几乎没有明显的炎症。门脉压在第 2 周时略有升高，在第 4 周时达到最大值[9.4 +/- 0.3 比 0 时的 2.9 +/- 0.6 mmHg（P=0.003）]，并在第 8 周时保持稳定。平均动脉血压（MABP）从第 2 周开始下降[第 4 周时的 98.7 +/- 5.7 mmHg 与第 0 周时的 123.8 +/- 1.8 mmHg（P=0.002）]。门静脉血流量从第 0 周的 1.85 +/- 0.11 增加到第 8 周的 3.07 +/- 0.44 ml/min/100 g（P=0.039）。肠系膜动脉血流量从第 0 周的 3.40 +/- 0.26 增加到第 8 周的 4.56 +/- 0.30 ml/min/100 g（P=0.043）。对 PE 的血管反应性从第 0 周的 138 +/- 3%逐渐下降到第 4 周的 110 +/- 5%（P=0.013）。