The Expression Of The Hif-vegf-notch Signaling Pathway-related Factors In The Kidney After Ischemic-reperfusion Iiyury(IRI)

Renal ischemia injury is in relation with body massive blood loss, renaloperation,renal transplantation and renal parenchyma lithotomy. As an importantpathological process, the timely reconstruction of renal blood flow in ischemic regionis a key treatment for renal ischemia reperfusion injury. HIF-VEGF and Notchsignaling pathway play important regulatory role in angiogenesis. Dll4as one of theNotch ligand, is an important angiogenesis regulatory factor. High expression ofVEGF can promote the expression of Dll4and Notch1. Renal ischemia reperfusioninjury can cause compensatory angiogenesis. Recently, studies have showed thatspecific miR-210can promote angiogenesis through the regulation of its target genesafter ischemia and hypoxia. We speculate that the HIF-VEGF-Notch signalingpathway may be the mainly signaling pathway for angiogenesis after renalischemia-reperfusion injury; MiR-210may be involved in the regulation ofHIF-VEGF-Notch signaling pathway to promote angiogenesis.By observing the expression of the HIF-VEGF-Notch signaling pathway-relatedfactors in the kidney after ischemic-reperfusion injury，We explore the mechanism ofangiogenesis in ischemic renal injury, the aim is to provide new ideas for thetreatment of ischemic renal injury.Methods：Twenty Balb/c mice were randomly divided into4groups，namelyischemia-reperfusion4h，1d，3d group(IR group)and sham operation group(shamgroup)．Mice were subjected to a standard renal I/R to induce acute kidney injury(AKI) after45min of bilateral renal artery clamping. After the operation for4h，1dand3d，mice were sacrificed and blood samples were obtained to examine the degreeof Creatinine(Cr)and Urea nitrogen(BUN)．Kidney samples were examined formiR-210、HIF-1α mRNA、VEGFmRNA、Dll4mRNA、Notch1mRNA、Hes1mRNAby quantitative Real-Time RT-PCR，HIF-1α、Notch1、Hes1protein by Westernblot．We confirmed that renal I/R injury model succeed based on biochemistrymeasurement and pathological level.Results：1Acute kidney injury model signs of success：The levels of Cr，BUN in IR4h and1d group were significantly increased compared to sham group，respectively is (40.2±3.5)，(90.00±3.81) μ mol/L，(16.88±1.31)，(38.86±5.11)mmol/L(P<0.05)； Renal tissue HE staining showed obvious pathologicalchanges.2.The expression of the HIF-VEGF-Notch signaling pathway-related factors inthe kidney after ischemic-reperfusion injury：In IR4h，1d and3d group，VEGF、Notch1，Hes1mRNA expression were significantly increased compared with Shamgroup(P<0.05)．The levels of HIF-1α、Dll4mRNA in IR4h and1d group weresignificantly increased compared to sham group(P<0.05)，which were obviouslydecreased in3d group；The levels of HIF-1α、Notch1and Hes1protein in IR4h，1d and3d group were increased apparently compared to Sham group(P<0.05)．Conclusion：The renal ischemia-reperfusion injury put an influence on theexpression of miR-210、HIF-1α、VEGF、Dll4、Notch1、Hes1．These results providedevidence that miR-210may be somehow involved in the mechanisms of renalischemic injury disease through targeting the HIF-VEGF-Notch signaling pathway toregulate angiogenesis.