title: Effect of donor JNK signal transduction inhibition on transplant outcome in brain dead rat model.
abstract: Renal grafts from brain-dead donors compared to living donors have a significantly shortened survival time due to heightened renal immunogenicity. The influence of pretreatment with a JNK signal transduction inhibitor on ischemia-reperfusion injury was examined in a renal transplant model using donors from a standardized rat model of brain death. Donors were treated immediately after induction of brain death with a JNK signal transduction inhibitor or saline. Kidney grafts from experimental group and control groups (saline-treated brain dead or living donor grafts) were examined serially up to 7 days post transplantation by morphology, immunohistology, and real-time PCR. JNK inhibition reduced the intensity of ischemia-reperfusion injury and acute rejection compared to saline treated donors. Likewise, cellular infiltration, mRNA transcription of some representative proinflammatory mediators and MHC-II molecules in the grafts were diminished in the JNK-inhibited donors compared to saline controls. Lewis rats transplanted with kidneys from JNK inhibited, brain-dead BN donors survived significantly longer than rats transplanted with saline treated brain-dead donors. The JNK inhibitor pretreatment of brain dead rats improved donor kidney quality, and improved graft survival.
authors.affiliation: Department of Urology, Changzheng Hospital, The Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.forename: Danfeng
authors.initials: D
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Gao
authors.forename: Xingang
authors.initials: X
authors.lastname: Cui
authors.forename: Zunguo
authors.initials: Z
authors.lastname: Du
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001926:Brain Death; D006084:Graft Rejection / Q000378:metabolism / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D016030:Kidney Transplantation; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D000873:Anthracenes; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases