Rosiglitazone Affects Nitric Oxide Synthases and Improves Renal Outcome in a Rat Model of Severe Ischemia/Reperfusion Injury

被引：37

作者：

Betz, Boris ^{[1
]}

Schneider, Reinhard ^{[1
]}

Kress, Tobias ^{[1
]}

Schick, Martin Alexander ^{[2
]}

Wanner, Christoph ^{[1
]}

Sauvant, Christoph ^{[3
]}

机构：

[1] Univ Klinikum Wurzburg, Med Klin & Poliklin 1, D-97080 Wurzburg, Germany

[2] Univ Klinikum Wurzburg, Klin & Poliklin Anasthesiol, D-97080 Wurzburg, Germany

[3] Univ Klinikum Halle Saale, Klin Anasthesie & Operat Intensivmed, D-06120 Halle, Saale, Germany

来源：

PPAR RESEARCH | 2012年 / 2012卷

关键词：

ACTIVATED-RECEPTOR-GAMMA; ISCHEMIA-REPERFUSION INJURY; FAILURE; KIDNEY; AGONISTS; INOS; PIOGLITAZONE; DYSFUNCTION; DEFICIENCY; PROTECTION;

D O I：

10.1155/2012/219319

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Background. Nitric oxide (NO)-signal transduction plays an important role in renal ischemia/reperfusion (I/R) injury. NO produced by endothelial NO-synthase (eNOS) has protective functions whereas NO from inducible NO-synthase (iNOS) induces impairment. Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor (PPAR)-gamma agonist exerted beneficial effects after renal I/R injury, so we investigated whether this might be causally linked with NOS imbalance. Methods. RGZ (5 mg/kg) was administered i.p. to SD-rats (f) subjected to bilateral renal ischemia (60 min). Following 24 h of reperfusion, inulin-and PAH-clearance as well as PAH-net secretion were determined. Morphological alterations were graded by histopathological scoring. Plasma NOx-production was measured. eNOS and iNOS expression was analyzed by qPCR. Cleaved caspase 3 (CC3) was determined as an apoptosis indicator and ED1 as a marker of macrophage infiltration in renal tissue. Results. RGZ improves renal function after renal I/R injury (PAH-/inulin-clearance, PAH-net secretion) and reduces histomorphological injury. Additionally, RGZ reduces NOx plasma levels, ED-1 positive cell infiltration and CC3 expression. iNOS-mRNA is reduced whereas eNOS-mRNA is increased by RGZ. Conclusion. RGZ has protective properties after severe renal I/R injury. Alterations of the NO pathway regarding eNOS and iNOS could be an explanation of the underlying mechanism of RGZ protection in renal I/R injury.

引用

页数：12

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