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大鼠肝移植后移植肝充血的不良反应及肝细胞生长因子的改善作用

Adverse effects of graft congestion and ameliorative effects of hepatocyte growth factor after liver transplantation in rats.

作者信息

Aoki Hikaru, Ito Takashi, Hirata Masaaki, Okumura Shinya, Masano Yuki, Ogawa Eri, Haga Hironori, Hatano Etsuro

机构信息

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.

出版信息

Liver Transpl. 2025 Jan 1;31(1):11-23. doi: 10.1097/LVT.0000000000000449. Epub 2024 Sep 3.

Abstract

Living donor liver transplantation (LT) and deceased donor split-LT often result in congestion within liver grafts. The regenerative process and function of congested areas, especially graft congestion associated with LT, are not well understood. Therefore, we created new rat models with congested areas in partially resected livers and orthotopically transplanted these livers into syngeneic rats to observe liver regeneration and function in congested areas. This study aimed to compare liver regeneration and the function of congested areas after liver resection and LT, and to explore a new approach to ameliorate the adverse effects of graft congestion. Although the congested areas after liver resection regenerated normally on postoperative day 7, the congested areas after LT had poor regeneration with abscess development on postoperative day 7. Necrotic areas in congested areas were larger after LT than after liver resection on postoperative days 1, 3, and 7 ( p < 0.05, p < 0.05, and p < 0.01, respectively). Although congested areas after liver resection did not affect survival, in the LT model, the survival of rats with congested areas was significantly poorer even with larger grafts than that of rats with smaller noncongested grafts ( p = 0.04). Hepatocyte growth factor administration improved the survival rate of rats with congested grafts from 41.7% to 100%, improved the regeneration of congested areas, and significantly reduced the size of necrotic areas ( p < 0.05). Thus, congested areas in liver grafts may negatively impact recipients. Short-term administration of hepatocyte growth factor may improve postoperative outcomes of recipients with graft congestion and contribute to more effective use of liver grafts (approval number: MedKyo-23137, Institutional Ethics Committee/Kyoto University).

摘要

活体供肝肝移植(LT)和尸体供肝劈离式肝移植常常导致肝移植物内出现充血。充血区域的再生过程和功能,尤其是与肝移植相关的移植物充血,目前尚未得到充分了解。因此,我们创建了部分肝切除后出现充血区域的新型大鼠模型,并将这些肝脏原位移植到同基因大鼠体内,以观察充血区域的肝脏再生和功能。本研究旨在比较肝切除和肝移植后充血区域的肝脏再生及功能,并探索一种新方法来改善移植物充血的不良影响。尽管肝切除后充血区域在术后第7天正常再生,但肝移植后充血区域在术后第7天再生不良且出现脓肿。术后第1天、3天和7天,肝移植后充血区域的坏死面积大于肝切除后(分别为p<0.05、p<0.05和p<0.01)。尽管肝切除后的充血区域不影响生存,但在肝移植模型中,即使移植物较大,有充血区域的大鼠的生存率仍显著低于移植物无充血且较小的大鼠(p = 0.04)。给予肝细胞生长因子可将有充血移植物大鼠的生存率从41.7%提高到100%,改善充血区域的再生,并显著减小坏死区域的大小(p<0.05)。因此,肝移植物中的充血区域可能对受体产生负面影响。短期给予肝细胞生长因子可能改善有移植物充血受体的术后结局,并有助于更有效地利用肝移植物(批准文号:MedKyo - 23137,京都大学机构伦理委员会)。

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