title: Naked caspase 3 small interfering RNA is effective in cold preservation but not in autotransplantation of porcine kidneys.
abstract: BACKGROUND
  Caspase 3 associated with apoptosis and inflammation plays a key role in ischemia-reperfusion injury. The efficacy of naked caspase 3 small interfering RNA (siRNA) has been proved in an isolated porcine kidney perfusion model but not in autotransplantation.
  
  
  METHODS
  The left kidney was retrieved from mini pigs and infused with the University of Wisconsin solution with or without 0.3mg of caspase 3 siRNA into the renal artery with the renal artery and vein clamped for 24-h cold storage (CS). After right nephrectomy, the left kidney was autotransplanted into the right for 48 h without systemic treatment of siRNA.
  
  
  RESULTS
  Fluorescent dye-labeled caspase 3 siRNA was visualized in the post-CS kidneys but was weakened after transplantation. The expression of caspase 3 messenger RNA and precursor was downregulated by siRNA in the post-CS kidneys. In the siRNA-preserved posttransplant kidneys, however, the caspase 3 messenger RNA and active subunit were upregulated with further decreased precursor but increased active caspase 3+ cells, apoptotic cells, and myeloperoxidase+ cells. Moreover, the renal tissue damage was aggravated by siRNA, whereas the renal function was not significantly changed.
  
  
  CONCLUSIONS
  Naked caspase 3 siRNA administered into the kidney was effective in cold preservation but not enough to protect posttransplant kidneys, which might be because of systemic complementary responses overcoming local effects.
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.forename: Yichen
authors.initials: Y
authors.lastname: Jia
authors.forename: Tian
authors.initials: T
authors.lastname: Zhao
authors.forename: Yinjia
authors.initials: Y
authors.lastname: Xue
authors.forename: Zitong
authors.initials: Z
authors.lastname: Zhao
authors.forename: Junlin
authors.initials: J
authors.lastname: Zhang
authors.forename: Jina
authors.initials: J
authors.lastname: Wang
authors.forename: Xuanchuan
authors.initials: X
authors.lastname: Wang
authors.forename: Yongyin
authors.initials: Y
authors.lastname: Qiu
authors.forename: Miao
authors.initials: M
authors.lastname: Lin
authors.forename: Dong
authors.initials: D
authors.lastname: Zhu
authors.forename: Guisheng
authors.initials: G
authors.lastname: Qi
authors.forename: Yue
authors.initials: Y
authors.lastname: Qiu
authors.forename: Qunye
authors.initials: Q
authors.lastname: Tang
authors.forename: Ruiming
authors.initials: R
authors.lastname: Rong
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Sujie
authors.initials: S
authors.lastname: Ni
authors.forename: Bin
authors.initials: B
authors.lastname: Lai
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nicholson
authors.forename: Tongyu
authors.initials: T
authors.lastname: Zhu
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D053148:Caspase 3 / Q000235:genetics* / Q000378:metabolism; D050377:Cold Ischemia / Q000379:methods*; D015536:Down-Regulation / Q000187:drug effects*; D020287:In Situ Nick-End Labeling; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine; D014182:Transplantation, Autologous / Q000379:methods
chemical_list: D015415:Biomarkers; D034741:RNA, Small Interfering; D053148:Caspase 3