肝动脉缓冲效应在促进肝硬化肝脏PVE术后肝再生的作用及其机制研究

The insufficient regeneration of cirrhotic liver after portal vein embolization (PVE) is a prominent problem in the hepatobiliary surgical field. Presently, most studies consider the portal vein as the target and research focus for promoting residual liver regeneration after PVE but neglect the role of hepatic artery in liver regeneration. Hepatic arterial buffer response (HABR) is an important mechanism for regulating hepatopetal blood flow. The increase of portal vein blood flow will lead to the reduction of hepatic artery blood flow caused by contraction, but there is no complementary relationship between them. The change of hepatic artery blood flow can not affect the portal vein blood flow. Hence, we hypothesized that we may take the HABR as a cut-in point, increase hepatic artery blood flow to promote the residual cirrhotic liver regeneration after PVE. To verify this hypothesis, we will build the rabbit model of cirrhosis, perform hepatic artery embolization and PVE sequentially, transfuse adenosine via the gastroduodenal artery to dilate hepatic artery and increase its blood flow, to achieve the goal of promoting the regeneration of cirrhotic liver after PVE, and mainly investigate the mechanism about influence of the change of shearing stress caused by hepatic artery blood flow on liver regeneration after PVE. Our study is expected to provide a new idea and a new targeting point to resolve the difficult problem of insufficient regeneration of cirrhotic liver after PVE.

肝硬化肝脏在门静脉栓塞术（PVE）后肝再生不足是肝胆外科领域面临的突出问题。目前绝大部分研究都将门静脉作为促进PVE术后剩余肝体积再生的作用靶点和研究重心，却忽略了肝动脉在肝再生中的作用。肝动脉缓冲效应（HABR）是调控入肝血流量的重要机制。门静脉血流量的增加会引发肝动脉收缩以减少血流灌注，但两者之间并不存在互补关系，肝动脉血流的变化并不会影响门静脉血流。我们提出了“以HABR为切入点，通过增加肝动脉血流量，促进肝硬化肝脏PVE术后剩余肝组织再生”的假说。为证实这一假说，本课题拟通过复制兔的肝硬化模型，先后行肝动脉栓塞和PVE术，术后经胃十二指肠动脉输注腺苷以扩张肝动脉，增加肝动脉血流量，以期达到促进肝硬化肝脏PVE术后肝再生的目的，并重点探讨肝动脉血流量改变所致的剪切应力变化影响PVE术后肝再生的作用机制。我们的研究有望为解决肝硬化肝脏PVE术后肝再生不足这一难题提供一种新思路和新靶点。

目前完成计划研究项目.本研究通过构建兔的肝硬化疾病模型，并先后行选择性肝动脉栓塞术（TAE）和门静脉栓塞术（PVE），并在实验研究中转用不同剂量的前列腺素，试图通过增加残肝肝动脉血流量，促进兔的肝硬化肝脏剩余肝组织再生。研究结果表明，注射前列腺素可增加兔肝硬化肝脏行TAE及PVE术后残肝动脉血流量及残肝的重量，并在细胞及分子层面观察到药物促进残肝再生的证据。该研究结果进一步证实了，肝硬化肝脏在行TAE及PVE术后存在残肝再生不足的事实。但是该研究也显示，通过局部运用血管活性药物（如前列腺素）可增加残肝动脉血流量，继而适当促进肝硬化肝脏行TAE及PVE术后残肝再生。有望在临床实践中通过药物干预解决肝硬化肝脏残肝再生不足这一临床难题，扩大肝硬化肝脏手术治疗的适应症，为肝硬化患者需行肝切除根治性治疗提供治疗的新方法。