Department of Urology, Second Affiliated Hospital of Nanchang University, Nanchang, PR China.
J Surg Res. 2012 Nov;178(1):460-5. doi: 10.1016/j.jss.2012.01.012. Epub 2012 Apr 4.
Renal ischemia-reperfusion injury (IRI) is a complex pathophysiologic process involving cell apoptosis and oxidant damages that leads to acute renal failure in both native kidneys and renal allografts. Pioglitazone is a novel class of oral antidiabetic agents currently used to treat type 2 diabetes mellitus. Pioglitazone exerts protective effects on acute myocardial ischemia and acute cerebral ischemia. The aim of this study was to investigate the possible beneficial effects of pioglitazone on renal IRI in mice.
IRI was induced by bilateral renal ischemia for 45 min followed by reperfusion. Fifty-five healthy male Balb/c mice were randomly assigned to one of the following groups: PBS + IRI, pioglitazone + IRI, PBS + sham IRI, pioglitazone + sham IRI. Kidney function tests, histopathologic examination, renal cell Bcl-2, and Bax expression were determined 24 h after reperfusion. Animals' survival was examined 7 days after operation.
Animals pretreated with pioglitazone had lower plasma levels of blood urea nitrogen and creatinine caused by IRI, lower histopathologic scores, and improved survival rates following IRI. Renal cell apoptosis induced by IRI was abrogated in kidneys of mice pretreated by pioglitazone, with an increase in Bcl-2 expression and a decrease in Bax expression. Furthermore, pioglitazone pretreatment protected against lethal renal IRI.
Peroxisome proliferator-activated receptor activation by pioglitazone exerts protective effects on renal IRI in mice by abrogating renal cell apoptosis. Thus, pioglitazone could be a novel therapeutic tool in renal IRI.
肾缺血再灌注损伤（IRI）是一种涉及细胞凋亡和氧化损伤的复杂病理生理过程，可导致原肾和肾移植发生急性肾衰竭。吡格列酮是一种新型的口服降糖药，目前用于治疗 2 型糖尿病。吡格列酮对急性心肌缺血和急性脑缺血具有保护作用。本研究旨在探讨吡格列酮对小鼠肾 IRI 的可能有益作用。
通过双侧肾缺血 45 分钟再灌注诱导 IRI。55 只健康雄性 Balb/c 小鼠随机分为以下几组：PBS+IRI、吡格列酮+IRI、PBS+假手术 IRI、吡格列酮+假手术 IRI。再灌注后 24 小时测定肾功能试验、组织病理学检查、肾细胞 Bcl-2 和 Bax 表达。术后 7 天观察动物的存活率。
吡格列酮预处理的动物的 IRI 引起的血尿素氮和肌酐水平较低，组织病理学评分较低，IRI 后生存率提高。吡格列酮预处理可减轻 IRI 诱导的肾细胞凋亡，增加 Bcl-2 表达，减少 Bax 表达。此外，吡格列酮预处理可预防致命性肾 IRI。
吡格列酮激活过氧化物酶体增殖物激活受体对小鼠肾 IRI 具有保护作用，可通过抑制肾细胞凋亡实现。因此，吡格列酮可能成为肾 IRI 的一种新的治疗工具。
