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胆管和门静脉结扎诱导的胆汁酸过载可提高大鼠分期肝切除术后的生存率。

Bile Acid Overload Induced by Bile Duct and Portal Vein Ligation Improves Survival after Staged Hepatectomy in Rats.

作者信息

Ge Xin-Lan, Zhang Xuan, Li Chong-Hui, Pan Ke, He Lei, Ren Wei-Zheng

机构信息

Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China.

Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, 100853, China.

出版信息

Curr Med Sci. 2023 Oct;43(5):1013-1022. doi: 10.1007/s11596-023-2779-5. Epub 2023 Oct 14.

Abstract

OBJECTIVE

Compared to portal vein ligation (PVL), simultaneous bile duct and portal vein ligation (BPL) can significantly enhance hypertrophy of the intact liver. This study aimed to investigate whether BPL could improve survival after extended hepatectomy independently of an increased remnant liver.

METHODS

We adopted rat models of 90% BPL or 90% PVL. To investigate the role of bile acids (BAs) the BA pools in the PVL and BPL groups were altered by the diet. Staged resection preserving 10% of the estimated liver weight was performed 3 days after BPL; PVL; or sham operation. Histology, canalicular network (CN) continuity; and hepatocyte polarity were evaluated.

RESULTS

At 3 days after BPL; PVL; or sham operation when the volumetric difference of the intended liver remained insignificant, the survival rates after extended hepatectomy were 86.7%, 47%, and 23.3%, respectively (P<0.01). BPL induced faster restoration of canalicular integrity along with an intensive but transient BA overload. Staged hepatectomy after BPL shortened the duration of the bile CN disturbance and limited BA retention. Decreasing the BA pools in the rats that underwent BPL could compromise these effects, whereas increasing the BA pools of rats that underwent PVL could induce similar effects. The changes in CN restoration were associated with activation of LKB1.

CONCLUSION

In addition to increasing the future remnant liver, BPL shortened the duration of the spatial disturbance of the CN and could significantly improve the tolerance of the hypertrophied liver to staged resection. BPL may be a safe and efficient future option for patients with an insufficient remnant liver.

摘要

目的

与门静脉结扎术(PVL)相比,同期胆管和门静脉结扎术(BPL)可显著增强残肝肥大。本研究旨在探讨BPL是否能独立于残肝增加而改善扩大肝切除术后的生存率。

方法

我们采用了90%BPL或90%PVL的大鼠模型。为了研究胆汁酸(BAs)的作用,通过饮食改变PVL组和BPL组的BA池。在BPL、PVL或假手术后3天进行分期切除,保留估计肝脏重量的10%。评估组织学、胆小管网络(CN)连续性和肝细胞极性。

结果

在BPL、PVL或假手术后3天,当预期肝脏的体积差异仍不显著时,扩大肝切除术后的生存率分别为86.7%、47%和23.3%(P<0.01)。BPL诱导胆小管完整性更快恢复,同时伴有强烈但短暂的BA过载。BPL后分期肝切除缩短了胆汁CN紊乱的持续时间并限制了BA潴留。减少接受BPL的大鼠的BA池会损害这些效应,而增加接受PVL的大鼠的BA池可诱导类似效应。CN恢复的变化与LKB1的激活有关。

结论

除了增加未来的残肝外,BPL缩短了CN空间紊乱的持续时间,并可显著提高肥大肝脏对分期切除的耐受性。BPL可能是残肝不足患者未来一种安全有效的选择。

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