IRAK-4-shRNA Prevents Ischemia/Reperfusion Injury Via Different Perfusion Periods Through the Portal Vein After Liver Transplantation in Rat
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Updated: Mar 13, 2026
Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model
Published on: April 2, 2017
1Department of Hepatobiliary Surgery, Suining Central Hospital, Sichuan, People's Republic of China.
Background:
This study analyzed the effects of short hairpin RNA targeting interleukin-1 receptor-associated kinase-4 (IRAK-4-shRNA) via portal vein perfusion during different periods on ischemia/reperfusion injury after liver transplantation.
Methods:
Rats were randomly divided into 3 groups: the cold ischemia transfection group (CIT group, n = 18), in which graft livers were perfused with the plasmid of pSIIRAK-4 expressing IRAK-4-shRNA for 4 minutes (0.5 mL/min) via the portal vein during the cold ischemia period; the in vivo transfection group (IVT group, n = 18), in which equivalent volumes (2 mL) of IRAK-4-ShRNA plasmid (pSIIRAK-4) were injected during the operation; and the control group (n = 18), in which the rats received equivalent volumes of blank plasmid. At 0, 60, and 180 minutes after portal vein reperfusion, blood and liver tissues were collected for examination. IRAK-4 expression, nuclear factor kB (NF-kB) activity, tumor necrosis factor α, interleukin (IL)-1β, and IL-6 serum levels, as well as histologic changes, were detected.
Results:
At 0 minutes after reperfusion, IRAK-4 expression, NF-κB activity, and serum levels of tumor necrosis factor α, IL-1β, and IL-6 showed no significant differences among the 3 groups (P > .05). At 60 and 180 minutes after reperfusion, all indices of the IVT and control groups were significantly higher than those of the CIT group (P < .01). Meanwhile, all indices of the CIT group showed no significant differences at various time points (P > .05). Liver function and histologic changes exhibited less liver injury in the CIT group than in the other groups.
Conclusions:
IRAK-4 activity was suppressed by IRAK-4-shRNA through portal vein perfusion during the cold ischemia period, and IRAK-4-shRNA effectively prevented ischemia/reperfusion injury after liver transplantation.
Insights
Short hairpin RNA targeting interleukin-1 receptor-associated kinase-4 (IRAK-4-shRNA) delivered during cold ischemia effectively prevented liver transplant injury. Portal vein perfusion of IRAK-4-shRNA during cold ischemia reduced ischemia/reperfusion injury in rats.
Area of Science:
- Transplantation immunology
- Molecular biology
- Surgical research
Background:
- Liver transplantation is susceptible to ischemia/reperfusion (I/R) injury.
- Interleukin-1 receptor-associated kinase-4 (IRAK-4) plays a role in inflammatory responses contributing to I/R injury.
Purpose of the Study:
- To investigate the efficacy of short hairpin RNA targeting IRAK-4 (IRAK-4-shRNA) delivered via portal vein perfusion during cold ischemia on I/R injury after liver transplantation.
- To compare the effects of IRAK-4-shRNA administration during cold ischemia versus in vivo administration.
Main Methods:
- Rats underwent liver transplantation and were divided into three groups: cold ischemia transfection (CIT), in vivo transfection (IVT), and control.
- IRAK-4-shRNA or blank plasmid was administered via portal vein perfusion (CIT) or injection (IVT) during different periods.
- IRAK-4 expression, NF-κB activity, inflammatory cytokines (TNF-α, IL-1β, IL-6), and histological changes were assessed post-reperfusion.
Main Results:
- No significant differences were observed among groups at 0 minutes post-reperfusion.
- At 60 and 180 minutes, the IVT and control groups showed significantly higher IRAK-4 expression, NF-κB activity, and cytokine levels compared to the CIT group.
- The CIT group exhibited significantly reduced liver injury, improved liver function, and less severe histological damage.
Conclusions:
- Portal vein perfusion of IRAK-4-shRNA during the cold ischemia period effectively suppresses IRAK-4 activity.
- IRAK-4-shRNA administration during cold ischemia significantly mitigates ischemia/reperfusion injury following liver transplantation.
