Dataset Information

Effects of ischemic preconditioning on the systemic and renal hemodynamic changes in renal ischemia reperfusion injury.

ABSTRACT:

Background

Ischemic preconditioning (IPC) could protect against subsequent renal ischemia reperfusion injury (IRI). However, the mechanisms underlying IPC remain far from complete. Hence, we explored the effects of IPC on the renal and systemic hemodynamic changes, renal function and morphology, as well the involvement of endothelial and inducible nitric oxide synthase (eNOS/iNOS), and nitric oxide (NO).

Methods

Male Sprague-Dawley rats were randomly divided into five groups after right-side nephrectomy: Sham group (surgery without vascular clamping); IRI group (the left renal artery was clamped for 45 min); IPC group (pretreated with 15 min of ischemia and 10 min of reperfusion); IPC + vehicle group (administrated with 0.9% saline 5 min before IPC); and IPC + N(G)-nitro-L-arginine methylester (L-NAME) group (pretreated with L-NAME 5 min prior to IPC). The renal and systemic hemodynamic parameters, renal function and morphology, as well as eNOS, iNOS, and NO expression levels in the kidneys were measured at the indicated time points after reperfusion.

Results

IPC rats exhibited significant improvements in renal function, morphology, and renal artery blood flow (RABF), without obvious influence on the systemic hemodynamics and renal vein blood flow. Increased eNOS, iNOS, and NO expression levels were detected in the kidneys of IPC rats 24 h after reperfusion. Furthermore, the beneficial effects were fully abolished by the administration of L-NAME.

Conclusions

The results suggest that IPC contributes to early restoration of RABF, probably through eNOS/iNOS-mediated NO production, thereby alleviating the renal dysfunction and histological damage caused by IRI.

SUBMITTER: Ge YZ

PROVIDER: S-EPMC4396246 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Effects of ischemic preconditioning on the systemic and renal hemodynamic changes in renal ischemia reperfusion injury.

Ge Yu-Zheng YZ Wu Ran R Xin Hui H Liu Hao H Lu Tian-Ze TZ Zhao You-Cai YC Shen Jiang-Wei JW Hu Zhi-Kai ZK Yu Peng P Zhou Liu-Hua LH Xu Lu-Wei LW Xu Zheng Z Wu Jian-Ping JP Li Wen-Cheng WC Zhu Jia-Geng JG Jia Rui-Peng RP

International journal of clinical and experimental pathology 20150201 2

<h4>Background</h4>Ischemic preconditioning (IPC) could protect against subsequent renal ischemia reperfusion injury (IRI). However, the mechanisms underlying IPC remain far from complete. Hence, we explored the effects of IPC on the renal and systemic hemodynamic changes, renal function and morphology, as well the involvement of endothelial and inducible nitric oxide synthase (eNOS/iNOS), and nitric oxide (NO).<h4>Methods</h4>Male Sprague-Dawley rats were randomly divided into five groups after ...[more]

PMID: 25972999

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Project description:BackgroundAlthough AKI lacks effective therapeutic approaches, preventive strategies using preconditioning protocols, including caloric restriction and hypoxic preconditioning, have been shown to prevent injury in animal models. A better understanding of the molecular mechanisms that underlie the enhanced resistance to AKI conferred by such approaches is needed to facilitate clinical use. We hypothesized that these preconditioning strategies use similar pathways to augment cellular stress resistance.MethodsTo identify genes and pathways shared by caloric restriction and hypoxic preconditioning, we used RNA-sequencing transcriptome profiling to compare the transcriptional response with both modes of preconditioning in mice before and after renal ischemia-reperfusion injury.ResultsThe gene expression signatures induced by both preconditioning strategies involve distinct common genes and pathways that overlap significantly with the transcriptional changes observed after ischemia-reperfusion injury. These changes primarily affect oxidation-reduction processes and have a major effect on mitochondrial processes. We found that 16 of the genes differentially regulated by both modes of preconditioning were strongly correlated with clinical outcome; most of these genes had not previously been directly linked to AKI.ConclusionsThis comparative analysis of the gene expression signatures in preconditioning strategies shows overlapping patterns in caloric restriction and hypoxic preconditioning, pointing toward common molecular mechanisms. Our analysis identified a limited set of target genes not previously known to be associated with AKI; further study of their potential to provide the basis for novel preventive strategies is warranted. To allow for optimal interactive usability of the data by the kidney research community, we provide an online interface for user-defined interrogation of the gene expression datasets (http://shiny.cecad.uni-koeln.de:3838/IRaP/).

Project description:The kidneys are prone to developing ischemia reperfusion injury (IRI) following certain renal surgeries and cardiovascular surgeries requiring cardiac arrest. Sevoflurane and ischemic preconditioning reportedly alleviate IRI, which is mediated via microRNAs. The present study compared anesthetic preconditioning (APC) and ischemic preconditioning (IPC) on microRNAs, which promote cell‑survival pathways in rats in a randomized controlled study. After undergoing right nephrectomy under general anesthesia, male Wistar rats (336±24 g) and were divided into four groups (IRI, APC, IPC and sham; n=7 each). The IRI group underwent 45 min clamping of the left renal vasculature, followed by 4 h of reperfusion. APC involved exposure to one minimum alveolar concentration sevoflurane for 15 min. IPC included three cycles of two‑min clamping and five‑min reperfusion. Blood and renal biopsy samples were assessed postoperatively to measure serum creatinine and to analyze renal microRNA (miR) expression using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) testing and their target pathways with Ingenuity Pathway Analysis™. The present study found that serum creatinine values in APC (0.71±0.08 mg/dl) and IPC (0.73±0.1 mg/dl) groups were lower than in the IRI group (0.96±0.13 mg/dl; P<0.05), indicating amelioration of IRI by APC and IPC. RT‑qPCR followed by pathway analysis indicated that APC and IPC affect 'protein kinase B (Akt)'. APC promoted miR‑17‑3p and suppressed miR‑27a. IPC promoted miR‑19a. All the miRs were predicted to regulate phosphorylated Akt, which promotes cell‑protection. Western blot analysis showed that expression of phosphorylated Akt increased and phosphatase and tensin homologue deleted from chromosome 10 (PTEN) decreased following APC and IPC. The present study concluded that APC and IPC affect different miRs, although they are estimated to similarly promote the PTEN/phosphoinositide 3‑kinase/Akt signaling pathway, resulting in reno‑protection.

Dataset Information

Effects of ischemic preconditioning on the systemic and renal hemodynamic changes in renal ischemia reperfusion injury.

Background

Methods

Results

Conclusions

Publications

Effects of ischemic preconditioning on the systemic and renal hemodynamic changes in renal ischemia reperfusion injury.

Similar Datasets

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