title: Remote ischemic perconditioning prevents liver transplantation-induced ischemia/reperfusion injury in rats: Role of ROS/RNS and eNOS.
abstract: OBJECTIVE
  To investigate the underlying mechanisms of the protective role of remote ischemic perconditioning (RIPerC) in rat liver transplantation.
  
  
  METHODS
  Sprague-Dawley rats were subjected to sham, orthotopic liver transplantation (OLT), ischemic postconditioning (IPostC) or RIPerC. After 3 h reperfusion, blood samples were taken for measurement of alanine aminotransferase, aspartate aminotransferase, creatinine (Cr) and creatinine kinase-myocardial band (CK-MB). The liver lobes were harvested for the following measurements: reactive oxygen species (ROS), H2O2, mitochondrial membrane potential (ΔΨm) and total nitric oxide (NO). These measurements were determined using an ROS/H2O2, JC1 and Total NOx Assay Kit, respectively. Endothelial NO synthase (eNOS) was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, and peroxynitrite was semi-quantified by western blotting of 3-nitrotyrosine.
  
  
  RESULTS
  Compared with the OLT group, the grafts subjected to RIPerC showed significantly improved liver and remote organ functions (P< 0.05). ROS (P< 0.001) including H2O2(P< 0.05) were largely elevated in the OLT group as compared with the sham group, and RIPerC (P< 0.05) reversed this trend. The collapse of ΔΨm induced by OLT ischemia/reperfusion (I/R) injury was significantly attenuated in the RIPerC group (P< 0.001). A marked increase of NO content and phosphoserine eNOS, both in protein and mRNA levels, was observed in liver graft of the RIPerC group as compared with the OLT group (P< 0.05). I/R-induced 3-nitrotyrosine content was significantly reduced in the RIPerC group as compared with the OLT group (P< 0.05). There were no significant differences between the RIPerC and IPostC groups for all the results except Cr. The Cr level was lower in the RIPerC group than in the IPostC group (P< 0.01).
  
  
  CONCLUSIONS
  Liver graft protection by RIPerC is similar to or better than that of IPostC, and involves inhibition of oxidative stress and up-regulation of the PI3K/Akt/eNOS/NO pathway.
authors.affiliation: Ning He, Jun-Jun Jia, Li Jiang, Yan-Fei Zhou, Bing-Yi Lin, Yi-Fan Peng, Jun-Jie Chen, Tian-Chi Chen, Rong-Liang Tong, Jian-Hui Li, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Ning
authors.initials: N
authors.lastname: He
authors.affiliation: Ning He, Jun-Jun Jia, Li Jiang, Yan-Fei Zhou, Bing-Yi Lin, Yi-Fan Peng, Jun-Jie Chen, Tian-Chi Chen, Rong-Liang Tong, Jian-Hui Li, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Jun-Jun
authors.initials: JJ
authors.lastname: Jia
authors.affiliation: Ning He, Jun-Jun Jia, Li Jiang, Yan-Fei Zhou, Bing-Yi Lin, Yi-Fan Peng, Jun-Jie Chen, Tian-Chi Chen, Rong-Liang Tong, Jian-Hui Li, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Li
authors.affiliation: Ning He, Jun-Jun Jia, Li Jiang, Yan-Fei Zhou, Bing-Yi Lin, Yi-Fan Peng, Jun-Jie Chen, Tian-Chi Chen, Rong-Liang Tong, Jian-Hui Li, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Zhou
authors.affiliation: Ning He, Jun-Jun Jia, Li Jiang, Yan-Fei Zhou, Bing-Yi Lin, Yi-Fan Peng, Jun-Jie Chen, Tian-Chi Chen, Rong-Liang Tong, Jian-Hui Li, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Bing-Yi
authors.initials: BY
authors.lastname: Lin
authors.affiliation: Ning He, Jun-Jun Jia, Li Jiang, Yan-Fei Zhou, Bing-Yi Lin, Yi-Fan Peng, Jun-Jie Chen, Tian-Chi Chen, Rong-Liang Tong, Jian-Hui Li, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Peng
authors.affiliation: Ning He, Jun-Jun Jia, Li Jiang, Yan-Fei Zhou, Bing-Yi Lin, Yi-Fan Peng, Jun-Jie Chen, Tian-Chi Chen, Rong-Liang Tong, Jian-Hui Li, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: Ning He, Jun-Jun Jia, Li Jiang, Yan-Fei Zhou, Bing-Yi Lin, Yi-Fan Peng, Jun-Jie Chen, Tian-Chi Chen, Rong-Liang Tong, Jian-Hui Li, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Tian-Chi
authors.initials: TC
authors.lastname: Chen
authors.affiliation: Ning He, Jun-Jun Jia, Li Jiang, Yan-Fei Zhou, Bing-Yi Lin, Yi-Fan Peng, Jun-Jie Chen, Tian-Chi Chen, Rong-Liang Tong, Jian-Hui Li, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Rong-Liang
authors.initials: RL
authors.lastname: Tong
authors.affiliation: Ning He, Jun-Jun Jia, Li Jiang, Yan-Fei Zhou, Bing-Yi Lin, Yi-Fan Peng, Jun-Jie Chen, Tian-Chi Chen, Rong-Liang Tong, Jian-Hui Li, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Ning He, Jun-Jun Jia, Li Jiang, Yan-Fei Zhou, Bing-Yi Lin, Yi-Fan Peng, Jun-Jie Chen, Tian-Chi Chen, Rong-Liang Tong, Jian-Hui Li, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Hai-Yang
authors.initials: HY
authors.lastname: Xie
authors.affiliation: Ning He, Jun-Jun Jia, Li Jiang, Yan-Fei Zhou, Bing-Yi Lin, Yi-Fan Peng, Jun-Jie Chen, Tian-Chi Chen, Rong-Liang Tong, Jian-Hui Li, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Ning He, Jun-Jun Jia, Li Jiang, Yan-Fei Zhou, Bing-Yi Lin, Yi-Fan Peng, Jun-Jie Chen, Tian-Chi Chen, Rong-Liang Tong, Jian-Hui Li, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Shu-Sen
authors.initials: SS
authors.lastname: Zheng
mesh_terms: D000818:Animals; D019194:Ischemic Preconditioning / Q000379:methods; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D053078:Membrane Potential, Mitochondrial; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat
keywords: Endothelial nitric oxide synthase; Ischemia/reperfusion injury; Liver transplantation; Reactive oxygen species; Remote ischemic perconditioning