Rosiglitazone affects nitric oxide synthases and improves renal outcome in a rat model of severe ischemia/reperfusion injury.
Rosiglitazone affects nitric oxide synthases and improves renal outcome in a rat model of severe ischemia/reperfusion injury.
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DOI：
10.1155/2012/219319
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发表时间：
2012
期刊：
影响因子：
2.9
通讯作者：
Sauvant C
中科院分区：
文献类型：
--
作者：
Betz B;Schneider R;Kress T;Schick MA;Wanner C;Sauvant C
背景一氧化氮（Nitric oxide，NO）信号转导在肾缺血再灌注损伤中起重要作用。内皮型一氧化氮合酶（eNOS）产生的一氧化氮具有保护作用，而诱导型一氧化氮合酶（iNOS）产生的一氧化氮则具有损伤作用。罗格列酮（RGZ）是一种过氧化物酶体增殖物激活受体（PPAR）-γ激动剂，在肾I/R损伤后发挥了有益作用，因此我们研究这是否可能与NOS失衡有关。方法.将RGZ（5 mg/kg）腹膜内给药于双侧肾缺血（60 min）的SD大鼠（f）。再灌注24小时后，测定菊糖和多环芳烃清除率以及多环芳烃净分泌。通过组织病理学评分对形态学改变进行分级。测定血浆NOx生成量。通过qPCR分析eNOS和iNOS表达。测定裂解型半胱天冬酶3（CC 3）作为细胞凋亡指标，测定ED 1作为肾组织中巨噬细胞浸润的标志物。结果RGZ改善肾I/R损伤后的肾功能（PAH-/菊粉-清除，PAH-净分泌），并减少组织形态学损伤。此外，RGZ降低NOx血浆水平、艾德-1阳性细胞浸润和CC 3表达。RGZ降低iNOS-mRNA，而增加eNOS-mRNA。结论RGZ在严重肾I/R损伤后具有保护作用。RGZ对肾I/R损伤的保护作用可能与NO通路中eNOS和iNOS的改变有关。
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)-γ 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.
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影响因子：
3.9
作者：
Canuelo, A.;Siles, E.;Martinez-Lara, E.
通讯作者：
Martinez-Lara, E.
影响因子：
--
作者：
Sauvant, Christoph;Schneider, Reinhard;Gekle, Michael
通讯作者：
Gekle, Michael
DOI：
10.1152/ajprenal.00341.2005
发表时间：
2006-05-01
影响因子：
4.2
作者：
Du, CG;Guan, QN;Jevnikar, AM
通讯作者：
Jevnikar, AM
臭氧氧化预处理保护大鼠肾脏免受再灌注损伤：一氧化氮的作用
影响因子：
2.2
作者：
Chen, Hui;Xing, Bianzhi;Chen, Zhiyuan
通讯作者：
Chen, Zhiyuan
影响因子：
9.5
作者：
Gonon, Adrian T.;Bulhak, Aliaksandr;Pernow, John
通讯作者：
Pernow, John