VEGF-C inhibits Kupffer cells activation and alleviates ischemia-reperfusion injury in rats after liver transplantation

Mingxiang CHENG; Jinzheng LI; Yong CHEN; Ding CAO; Jianping GONG; Bing TU; Bailin NIU

doi:10.16016/j.1000-5404.201810125

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VEGF-C inhibits Kupffer cells activation and alleviates ischemia-reperfusion injury in rats after liver transplantation

Basic Medicine | 更新时间：2026-01-09

- VEGF-C inhibits Kupffer cells activation and alleviates ischemia-reperfusion injury in rats after liver transplantation
- Journal of Third Military Medical University Vol. 41, Issue 7, Pages: 653-658(2019)
- 作者机构：
  
  1.400010 重庆，重庆医科大学附属第二医院肝胆外科
  2.400016 重庆，重庆医科大学附属第一医院：肝胆外科
  3.400016 重庆，重庆医科大学附属第一医院：急诊&重症医学科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81871261);the Project of Application Developmental Plan of Beibei District, Chongqing(2016-14)
- DOI：10.16016/j.1000-5404.201810125
  CLC： R-332;R617;R657.3
- Received：20 October 2018，
  
  Revised：2019-01-08，
  
  Published：15 April 2019
- 稿件说明：
移动端阅览
Mingxiang CHENG, Jinzheng LI, Yong CHEN, et al. VEGF-C inhibits Kupffer cells activation and alleviates ischemia-reperfusion injury in rats after liver transplantation[J]. Journal of Third Military Medical University, 2019, 41(7): 653-658.
DOI：

Mingxiang CHENG, Jinzheng LI, Yong CHEN, et al. VEGF-C inhibits Kupffer cells activation and alleviates ischemia-reperfusion injury in rats after liver transplantation[J]. Journal of Third Military Medical University, 2019, 41(7): 653-658. DOI： 10.16016/j.1000-5404.201810125.

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(

0.05)，而IL-10含量增加(

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(

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(

0.05)，而M2型基因水平及SOCS1/p-GSK3β的表达明显增高(

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.

Methods

Liver 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 bili

rubin (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).

Results

Compared with the controls

VEGF-C perfusion reduced serum ALT and TBIL levels

alleviated liver damage and suppressed the contents of proinflammatory cytokines (

0.05)

but increased IL-10 level (

0.05). The VEGFR-3 mRNA level in KCs was increased after reperfusion in both VEGF-C group and control group (

0.05) when compared with the sham operation group (

0.05). In KCs

the mRNA levels of M1 specific marker genes and NF-κB activity were significantly inhibited in VEGF-C group (

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 (

0.05).

Conclusion

Exogenous VEGF-C protects liver graft from IRI by regulating the inflammatory responses and modifying polarization of KCs.

关键词

Keywords

references

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