Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Clin Sci (Lond). 2018 Mar 26;132(6):669-683. doi: 10.1042/CS20171370. Print 2018 Mar 30.
Liver cirrhosis is characterized by portal hypertension. However, the alteration of portal hypertension-related derangements during cirrhosis resolution is not well known. The present study aimed to establish animal models with cirrhosis resolution and to investigate the relevant changes during this process. Male Sprague-Dawley rats were applied. In reverse thioacetamide (rTAA) model, rats were randomly allocated into four groups with control, thioacetamide (TAA) cirrhosis and rTAA groups that discontinued TAA for 4 or 8 weeks after cirrhosis induction. In reverse bile duct ligation (rBDL) model, rats received choledochoduodenal shunt surgery upon the establishment of cirrhosis and 4, 8, or 16 weeks were allowed after the surgery. At the end, portal hypertension-related parameters were evaluated. Cirrhosis resolution was observed in rTAA groups. Portal pressure (PP) decreased after cirrhosis resolution but remained higher than control group (control, TAA, rTAA4, rTAA8 (mmHg): 5.4 ± 0.3, 12.9 ± 0.3, 8.6 ± 0.4, 7.6 ± 0.6). Further survey found the increased splanchnic blood flow did not reduce during cirrhosis resolution. The extrahepatic pathological angiogenesis was not ameliorated (% of mesenteric window area: 1.2 ± 0.3, 7.3 ± 1.1, 8.3 ± 1.0, 11.3 ± 2.7). In collateral system, the shunting degree reduced while the vessels structure remained. The vascular contractility of all systems and nitric oxide (NO) production were normalized. In rBDL series, PP decreased in rBDL16 groups but the extrahepatic angiogenesis persisted. In conclusion, cirrhosis resolution attenuates but not completely normalizes portal hypertension because of persistently high splanchnic inflow and angiogenesis. In clinical setting, vascular complications such as varices could persist after cirrhosis resolution and further investigation to define the follow-up and treatment strategies is anticipated.
肝硬化的特征是门静脉高压。然而，肝硬化消退过程中门静脉高压相关紊乱的改变尚不清楚。本研究旨在建立肝硬化消退的动物模型，并探讨在此过程中的相关变化。雄性 Sprague-Dawley 大鼠被应用。在反硫代乙酰胺（rTAA）模型中，大鼠被随机分为四组：对照组、硫代乙酰胺（TAA）肝硬化组和 rTAA 组，rTAA 组在肝硬化诱导后停止 TAA 喂养 4 或 8 周。在反胆管结扎（rBDL）模型中，大鼠在建立肝硬化后接受胆总管十二指肠分流术，手术后分别允许 4、8 或 16 周。最后，评估了与门静脉高压相关的参数。rTAA 组观察到肝硬化消退。肝硬化消退后门静脉压力（PP）降低，但仍高于对照组（对照组、TAA 组、rTAA4 组、rTAA8 组（mmHg）：5.4±0.3、12.9±0.3、8.6±0.4、7.6±0.6）。进一步的调查发现，肝硬化消退过程中内脏血流增加并没有减少。肝外病理性血管生成没有改善（肠系膜窗面积百分比：1.2±0.3、7.3±1.1、8.3±1.0、11.3±2.7）。在侧支系统中，分流程度降低，而血管结构仍然存在。所有系统的血管收缩性和一氧化氮（NO）产生均恢复正常。在 rBDL 系列中，rBDL16 组的 PP 降低，但肝外血管生成仍然存在。总之，肝硬化消退可减轻但不能完全纠正门静脉高压，因为持续高内脏血流量和血管生成。在临床环境中，肝硬化消退后血管并发症如静脉曲张可能仍然存在，需要进一步研究以确定随访和治疗策略。
