Expression Of SDF-1 In The Acute Ischemia-reperfusion Injury And The Relationship Between SDF-1 And Macrophages

Objective The repair phase of renal ischemia-reperfusion(IR) injury mainly involves suppression of inflammation and proliferation of tubular epithelial cells. The macrophages undergo a switch from a proinflammatory to a tropic phenotype that supports the transition from tubular injury to tubular repair. To observe the expression of stromal cell-derived factor 1(SDF-1) in the kidney after ischemic reperfusion injury(IRI), and explore the relationship between SDF-1 and macrophage in the IRI kidney.Methods Totally of 96 healthy C57BL/6 male mice were established with clamping both pedicles for 35 min followed by reperfusion. Kidney samples were collected at indicated times. For histological examination, sections were stained with haematoxylin-eosin staining(H&E). The expression of ED-1, iNOS, Arg-1 was detected by immunohistochemistry staining and western blotting. The expression and site of SDF-1 were determined by immunohistochemistry, ELISA and RT-PCR, expression of CXCR4 was determined by immunohistochemistry staining and western blotting. After the clodronate liposome injected intraperitneally, the location of ED-1 was observed by immunohistochemistry and immunofluorescence staining, and renal histology and protein expression of SDF-1 were detected.Results Compared with sham-operated group, classical tubular damage and serious were found in IR injury group, accompanied by a large number of inflammatory cells. We show that M1 macrophage are recruited into the kidney in the early phase of IR injury, whereas M2 macrophages predominate at the later time points. The level of total renal SDF-1 peaked at Day 1 following ischemia compared with that in kidneys from sham-operated animals, and decreased to control levels in the following days. SDF-1 in healthy kidney is localized at cortex, whereas it’s expanded to the corticomesdullary area of the kidney during IR injury. Compared with IR injury groups, elimination of macrophage before IR injury by injection of liposomal clodronate alleviated renal IR injury and up-regulated the expression of SDF-1, whereas depletion at 3 days after injury slows tubular cell repair and proliferation and down-regulated the expression of SDF-1.Conclusions SDF-1 expression is up-regulated in IRI kidney and is associated with macrophage. SDF-1 is also increased in urine after IR injury and it may be a new marker in diagnosis of AKI. Targeting it could have therapeutic potential to improve repair after IR injury.