Donor graft interferon regulatory factor-1 gene transfer worsens liver transplant ischemia/reperfusion injury.
Donor graft interferon regulatory factor-1 gene transfer worsens liver transplant ischemia/reperfusion injury.
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DOI：
10.1016/j.surg.2009.06.011
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发表时间：
2009-08
期刊：
影响因子：
3.8
通讯作者：
Geller DA
中科院分区：
文献类型：
--
作者：
Kim KH;Dhupar R;Ueki S;Cardinal J;Pan P;Cao Z;Cho SW;Murase N;Tsung A;Geller DA
肝缺血再灌注损伤是肝移植后导致移植物功能障碍的一种现象。了解这一过程背后的分子机制对于制定预防短期和长期移植物功能障碍的策略至关重要。本研究的目的是探讨转录因子IRF-1在大鼠原位肝移植模型中的作用。在冷UW液中保存18或3小时后进行原位同基因LEW大鼠肝移植（奥尔特）。AdIRF-1或对照基因载体（Adnull）在移植物收获前4天通过供体静脉内预处理递送至肝脏。未感染的移植物也作为对照。移植后1至24小时处死受体。长期保存移植物（18小时）进行奥尔特的大鼠在1和3小时显示肝细胞核IRF-1蛋白表达增加。与Adnull预处理的供肝相比，移植前用AdIRF-1预处理的大鼠在短期移植物（3小时）中ALT水平升高，IFN-β、IFN-γ、IL-12和iNOS表达增加。AdIRF-1预处理的供体肝脏在移植的移植物中也表现出对早期凋亡的敏感性增加，并且裂解的caspase-3的TUNEL染色表达增加。此外，与Adnull预处理的供体肝脏相比，AdIRF-1预处理的供体肝脏具有增加的MAP激酶JNK活化。IRF-1是大鼠原位肝奥尔特后IR损伤的重要调节因子。靶向IRF-1可能是改善移植后缺血性肝损伤以最小化器官功能障碍的潜在策略。
Liver ischemia and reperfusion (IR) injury is a phenomenon that leads to graft dysfunction following liver transplantation. Understanding the molecular mechanisms behind this process is crucial to developing strategies to prevent short and long term graft dysfunction. The purpose of this study is to explore the role of the transcription factor, IRF-1, in a model of orthotopic rat liver transplantation. Orthotopic syngeneic LEW rat liver transplantation (OLT) was performed after 18 or 3 hours preservation in cold UW solution. AdIRF-1 or control gene vector (Adnull) was delivered to the liver by donor intravenous pretreatment 4 days before graft harvesting. Uninfected grafts also served as controls. Recipients were sacrificed 1 to 24 hours post-transplantation. Rats that underwent OLT with long-term preserved graft (18 hours) displayed increased hepatic nuclear expression of IRF-1 protein at 1 and 3 hours. Rats pre-treated with AdIRF-1 prior to transplantation had increased ALT levels and increased expression of IFN-β, IFN-γ, IL-12, and iNOS in short-term period graft(3 hours) when compared with donor livers pre-treated with Adnull. AdIRF-1 pre-treated donor livers also exhibited increased susceptibility to early apoptosis in the transplanted grafts with increased TUNEL staining expression of cleaved caspase-3. Additionally, AdIRF-1 pre-treated donor livers had increased activation of the MAP kinase JNK as compared with Adnull pre-treated donor livers. IRF-1 is an important regulator of IR injury after OLT in rats. Targeting of IRF-1 may be a potential strategy to ameliorate ischemic liver injury after transplantation in order to minimize organ dysfunction.
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影响因子：
6.2
作者：
Mueller, THJ;Kienle, K;Rentsch, M
通讯作者：
Rentsch, M
影响因子：
11.4
作者：
PINE, R;CANOVA, A;SCHINDLER, C
通讯作者：
SCHINDLER, C
人肝细胞中诱导型一氧化氮合酶的分子克隆和表达
DOI：
10.1073/pnas.90.8.3491
发表时间：
1993-04-15
影响因子：
11.1
作者：
GELLER, DA;LOWENSTEIN, CJ;BILLIAR, TR
通讯作者：
BILLIAR, TR
影响因子：
6.2
作者：
Chia, SH;Geller, DA;Murase, N
通讯作者：
Murase, N
影响因子：
6.2
作者：
FURUKAWA, H;TODO, S;STARZL, TE
通讯作者：
STARZL, TE