Ischemic
acute kidney injury (AKI) has always been a hot and difficult research topic in the field of renal diseases. This study aims to illustrate the safe
warm ischemia time of kidney and the molecular network characteristics and pathological features of mild to severe
ischemia reperfusion kidney injury. We established varying degrees of renal injury due to different
ischemia time (0 min, 16 min, 18 min, 20 min, 22 min, 24 min, 26 min, 28 min, and 30 min) on unilateral (left kidney)
ischemia-reperfusion injury and contralateral (right kidney) resection (uIRIx) mouse model. Mice were sacrificed 24 h after uIRIx, blood samples were harvested to detect serum
creatinine (Scr), and kidney tissue samples were harvested to perform
Periodic Acid-Schiff (PAS) staining and
RNA-Seq. Differentially expressed genes (DEGs) were identificated, time-dependent gene expression patterns and functional enrichment analysis were further performed. Finally, qPCR was performed to validated
RNA-Seq results. Our results indicated that there was no absolute safe renal
warm ischemia time, and every minute of
ischemia increases kidney damage.
Warm ischemia 26min or above in mice makes severe kidney injury, renal pathology and SCr were both significantly changed.
Warm ischemia between 18 and 26 min makes mild kidney injury, with changes in pathology and renal molecular expression, while SCr did not change. No obvious pathological changes but significant differences in molecular expression were found less than 16min
warm ischemia. There are two key time intervals in the process of renal
ischemia injury, 0 min-16 min (short-term) and 26 min-28 min (long-term). Gene expression of immune-related pathways were most significantly down-regulated in short-term
ischemia, while metabolism-related pathways were the mainly enriched pathway in long-term
ischemia. Taken together, this study provides novel insights into safe renal artery occlusion time in partial
nephrectomy, and is of great value for elucidating molecular network characteristics and pathological features of mild to severe
ischemia reperfusion kidney injury, and key genes related to metabolism and immune found in this study also provide potential diagnostic and therapeutic
biomarkers for AKI.