Sulikowski Tadeusz, Domanski Leszek, Ciechanowski Kazimierz, Adler Grazyna, Pawlik Andrzej, Safranow Krzysztof, Dziedziejko Violetta, Chlubek Dariusz, Ciechanowicz Andrzej
Department of General and Transplantation Surgery of Pomeranian Medical University, Szczecin, Poland.
Arch Med Res. 2008 May;39(4):459-62. doi: 10.1016/j.arcmed.2008.01.005.
Ischemia/reperfusion (I/R) injury is often responsible for delayed graft function after transplantation. Trimetazidine (TMZ) is an anti-ischemic and antioxidant agent used to protect grafts from I/R injury. With the supply of molecular oxygen upon reperfusion of ischemic tissues, xanthine oxidoreductase (XOR) metabolizes xanthine and hypoxanthine to uric acid and free radicals are generated. The aim of the study was to examine the effect of TMZ on XOR expression in rat kidney with I/R injury. The study was carried out on Wistar rats divided into two groups: animals treated with TMZ and control group receiving placebo. TMZ (10 mg/kg/day) was administered for 30 days. There were no significant differences in XOR expression in kidneys without ischemia between rats treated with TMZ and control group, whereas the XOR expression in kidneys with ischemia was significantly decreased in rats treated with TMZ as compared with control animals. The XOR expression in ischemic kidney was significantly lower in comparison with kidney without ischemia in the group treated with TMZ. We suggest that the decrease in xanthine oxidoreductase expression is one of the beneficial mechanisms of TMZ on I/R injury, preventing the degradation of purine nucleotides during the oxidation of hypoxanthine to xanthine and uric acid and formation of free radicals.
缺血/再灌注（I/R）损伤常导致移植后移植物功能延迟。曲美他嗪（TMZ）是一种抗缺血和抗氧化剂，用于保护移植物免受I/R损伤。随着缺血组织再灌注时分子氧的供应，黄嘌呤氧化还原酶（XOR）将黄嘌呤和次黄嘌呤代谢为尿酸，并产生自由基。本研究的目的是探讨TMZ对I/R损伤大鼠肾脏中XOR表达的影响。该研究在Wistar大鼠上进行，分为两组：接受TMZ治疗的动物和接受安慰剂的对照组。TMZ（10mg/kg/天）给药30天。在未发生缺血的大鼠中，TMZ治疗组和对照组肾脏中XOR的表达无显著差异，而与对照动物相比，TMZ治疗的缺血大鼠肾脏中XOR的表达显著降低。在TMZ治疗组中，缺血肾脏中的XOR表达明显低于未缺血的肾脏。我们认为，黄嘌呤氧化还原酶表达的降低是TMZ对I/R损伤的有益机制之一，可防止次黄嘌呤氧化为黄嘌呤和尿酸过程中嘌呤核苷酸的降解以及自由基的形成。
