Evidence for a protective role of trimetazidine during cold ischemia: targeting inflammation and nephron mass

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• 作者：Faure ; Jean-Pierre ; Baumert ; Herve ; Han ; Zeqiu ; Goujon ; Jean Michel ; Favreau ; Frederic ; Dutheil ; Delphine ; et. al.
• 关键词：CEL ; Celsior solution ; CEL24hr ; 24hr of cold ischemia in CEL ; CEL48hr ; 48hr of cold ischemia in CEL ; CEL72hr ; 72hr of cold ischemia in CEL ; CELTMZ24hr ; 24hr of cold ischemia in CEL plus TMZ ; CELTMZ48hr ; 48hr of cold ischemia in CEL plus TMZ ; CELTMZ72hr ; 7
• 刊名：Biochemical Pharmacology
• 出版年：2003
• 出版时间：December 1, 2003
• 年：2003
• 卷：66
• 期：11
• 页码：2241-2250
• 全文大小：460 K

文摘

Ischemia–reperfusion injury (IRI) is associated with an increased risk of acute rejection, delayed graft function, or chronic graft dysfunction. Mitochondria plays a central role in this process. Using an autotransplant pig kidney model, changes in renal function and morphology were determined after different periods of cold ischemia in kidneys preserved in the University of Wisconsin solution (UW), high-Na⁺ version of UW (HEH) or Celsior (CEL) a newly developed high-Na⁺ solution, with or without trimetazidine (TMZ). Kidney function was better preserved in HEH after 24hr and particularly 48- and 72-hr cold storage than in CEL and UW. TMZ improved the preservation quality when added to the different solutions tested, particularly after 48- and 72-hr cold storage. Interstitial fibrosis and tubular atrophy were reduced in HEH with TMZ. CD4⁺ T-cell infiltration was also modulated by the preservation conditions. Peripheral-type benzodiazepine receptor (PBR) positive cells infiltration was also modulated by preservation conditions. TMZ was efficient to reduce IRI when added in the various preservation solutions. These results suggest that protection of the mitochondrial function should be a major target to limit IRI. In addition, this study outlines the role of CD4⁺ T cells and PBR expression in inflammatory responses after IRI.