Protective Effects of Ischemic Preconditioning-Mediated Homing of Endothelial Progenitor Cells on Renal Acute Ischemia and Reperfusion Injury in Male Rats
Jianxin Xue, Zhiqiang Qin, Xiao Li, Pu Cao, Ruipeng Jia
(Department of Urology, The Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu, China (mainland))
Ann Transplant 2017; 22:66-74
The objective of this study was to determine whether homing of endothelial progenitor cells (EPCs) induced by ischemic preconditioning (IPC) contributed to the protection of renal acute ischemia-reperfusion injury (IRI) in male rats.
MATERIAL AND METHODS: Forty male Sprague-Dawley rats were randomly divided into four groups, including sham-operated group, IRI-operated group, IPC-treated group and EPCs-treated group. Subsequently, serum samples were collected at 24 and 72 hours after reperfusion, respectively. In addition, histological examination was utilized to assess changes in renal structure. Moreover, immunohistochemical staining, quantitative real-time PCR and Western blotting analysis detected the expression levels of CD31, CD34, vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2).
RESULTS: Rats in the EPCS-treated group had significantly reduced levels of blood urea nitrogen and serum creatinine at 24 hours after operation, compared to rats that in the IRI-operated group. At 72 hours after reperfusion, renal function and morphology showed significant improvements in the EPCs-treated group. In addition, CD31+ and CD34+ cells that mostly accumulated in the renal medulla were significantly increased in IPC-treated group at 72 hours (p<0.05). Compared to the IRI-operated group, the number of EPCs in the kidneys was markedly increased at 72 hours following reperfusion in the IPC-treated group. In addition, expression levels of VEGF, Ang-1 and Ang-2 in the kidneys of the IPC-treated and EPCs-treated rats were significantly increased compared to the IRI-operated group.
CONCLUSIONS: These results provided evidence that IPC-mediated homing of EPCs played an important role in the protection of renal acute IRI, involving promotion of cell proliferation and angiogenesis through release of several angiogenic factors, such as VEGF, Ang-1, and Ang-2.
Keywords: Ischemic Preconditioning, Receptors, Vascular Endothelial Growth Factor, Reperfusion Injury