[1]成名翔,李金政,陈勇,等.VEGF-C抑制Kupffer细胞激活减轻大鼠肝移植缺血再灌注损伤[J].第三军医大学学报,2019,41(07):653-658.
 CHENG Mingxiang,LI Jinzheng,CHEN Yong,et al.VEGF-C inhibits Kupffer cells activation and alleviates ischemiareperfusion injury in rats after liver transplantation [J].J Third Mil Med Univ,2019,41(07):653-658.
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VEGF-C抑制Kupffer细胞激活减轻大鼠肝移植缺血再灌注损伤(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
41卷
期数:
2019年第07期
页码:
653-658
栏目:
基础医学
出版日期:
2019-04-15

文章信息/Info

Title:
VEGF-C inhibits Kupffer cells activation and alleviates ischemiareperfusion injury in rats after liver transplantation
 
作者:
成名翔李金政陈勇曹丁龚建平涂兵钮柏琳
重庆医科大学附属第二医院肝胆外科;重庆医科大学附属第一医院:肝胆外科,急诊&重症医学科
Author(s):
CHENG Mingxiang LI Jinzheng CHEN Yong CAO Ding GONG Jianping TU Bing NIU Bailin  

Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010; Department of Hepatobiliary Surgery, Department of Emergency & Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
 

 

关键词:
肝脏移植缺血再灌注损伤血管内皮生长因子C血管内皮生长因子受体-3Kupffer细胞  
Keywords:
liver transplantation ischemia reperfusion injuryvascular endothelial growth factor-c vascular endothelial growth factor receptor-3 Kupffer cells
分类号:
R-332; R617; R657.3
文献标志码:
A
摘要:

目的 阐明血管内皮生长因子受体-3(vascular endothelial growth factor receptor-3, VEGFR-3) /血管内皮生长因子c (vascular endothelial growth factor-c, VEGF-C)信号能否抑制Kupffer细胞(KCs)活化并减轻移植肝脏缺血再灌注损伤(ischemia reperfusion injury, IRI)。方法建立LewisLewis大鼠肝移植模型,分为VEGF-C组(6 对,在冷保存期经门静脉灌注VEGF-C)、对照组(6对,灌注等体积UW液)、假手术组(6只)。术后24 h处死动物,检测血清中丙氨酸氨基转移酶(ALT)、总胆红素(TBIL)、炎症因子水平,并进行病理学分析。分离KCs,RT-PCR检测VEGFR-3及极化特异性标记基因水平,EMSA检测NFκB转录活性,Western blot检测细胞因子信号传导抑制因子1 (suppressor of cytokine signaling 1, SOCS1)和磷酸化糖原合成酶激酶3β(phosphorylated glycogen synthase kinase 3β, p-GSK3β)的表达。结果 VEGF-C组中ALT和TBIL水平、肝脏损伤程度、促炎因子水平均较对照组降低(P<0.05),而IL-10含量增加(P<0.05)。VEGFC组和对照组KCs中VEGFR-3的mRNA水平明显高于假手术组(P<0.05)。VEGF-C组KCs中M1型基因表达、NFκB活性较对照组明显降低(P<0.05),而M2型基因水平及SOCS1/pGSK3β的表达明显增高(P<0.05)。 结论VEGF-C通过抑制炎症反应和调节KCs极化从而减轻移植肝脏IRI

 

Abstract:

Objective To investigate whether vascular endothelial growth factor receptor-3 (VEGFR-3)/VEGF-C signaling suppresses activation of Kupffer cells (KCs) and attenuates hepatic ischemia-reperfusion injury (IRI) after liver transplantation. MethodsLiver transplantation model was established in 12 pairs of Lewis-Lewis rats, 6 pairs for VEGF-C group and the other for control group. The donor livers of the VEGF-C group were perfused with VEGF-C injection via portal vein during cold preservation, while those of control group were perfused with UW solution. Another 6 rats served as sham operation group. In 24 h after transplantation, all rats were sacrificed, and serum levels of alanine transaminase (ALT), total bilirubin (TBIL) and inflammatory cytokines, as well as histological changes were detected and observed. KCs were isolated from the grafts. RT-PCR was used to evaluate the expression of VEGFR-3 and polarization-specific marker genes, EMSA was utilized to quantify the nuclear factor-κB (NF-κB) transcriptional activity, and Western blotting was employed to assess the expression of suppressor of cytokine signaling 1(SOCS1) and phosphorylated glycogen synthase kinase 3β (p-GSK3β). ResultsCompared with the controls, VEGF-C perfusion reduced serum ALT and TBIL levels, alleviated liver damage and suppressed the contents of proinflammatory cytokines (P<0.05), but increased IL-10 level (P<0.05). The VEGFR-3 mRNA level in KCs was increased after reperfusion in both VEGF-C group and control group (P<0.05) when compared with the sham operation group (P<0.05). In KCs, the mRNA  levels of M1 specific marker genes and NF-κB activity were significantly inhibited in VEGF-C group (P<0.05), while the mRNA levels of M2 specific marker genes and the expression of SOCS1 and p-GSK3β were enhanced when compared with control group (P<0.05). ConclusionExogenous VEGF-C protects liver graft from IRI by regulating the inflammatory responses and modifying polarization of KCs.

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更新日期/Last Update: 2019-04-05