title: IRAK-4-shRNA Prevents Ischemia/Reperfusion Injury Via Different Perfusion Periods Through the Portal Vein After Liver Transplantation in Rat.
abstract: 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.
authors: Department of Hepatobiliary Surgery, Suining Central Hospital, Sichuan, People's Republic of China.
authors: Y
authors: Y
authors: Wu
authors: Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
authors: Y
authors: Y
authors: Liu
authors: Department of Hepatobiliary Surgery, Suining Central Hospital, Sichuan, People's Republic of China.
authors: M
authors: M
authors: Li
authors: Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
authors: Z
authors: Z
authors: Liu
authors: Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China. Electronic address: gongjianping1111@163.com.
authors: J
authors: J
authors: Gong
mesh_terms: D000818:Animals; D050377:Cold Ischemia; D007262:Infusions, Intravenous; D053592:Interleukin-1 Receptor-Associated Kinases / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D011169:Portal Vein / Q000473:pathology; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D015398:Signal Transduction; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D053592:Interleukin-1 Receptor-Associated Kinases