Abstract: FR-PO090
The Effect and Mechanism of Leptin in Ischemia Reperfusion Induced AKI
Session Information
- AKI: Tubules, Metabolism, New Models
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Li, Siyao, Second Xiangya Hospital Central South University, Changsha, China
- Xi, Jing, Second Xiangya Hospital Central South University, Changsha, China
- He, Yi, Second Xiangya Hospital Central South University, Changsha, China
- Chen, Junxiang, Second Xiangya Hospital Central South University, Changsha, China
Background
Ischemia-reperfusion (IR)-induced acute kidney injury (AKI) is one of the most common causes of AKI, but the underlying pathogenesis is poorly understood. And there are little reports about the role of leptin in IR-induced AKI.
Methods
Bilateral renal ischemia (30 min)/reperfusion (48hrs) injury (IRI) model was performed using ob/+ mice (wild type) and ob/ob mice (Leptin deficient). Blood samples were collected for renal function evaluation and the kidneys were removed for histological examination and protein detection.
Results
Compared with the sham groups, both of the I/R groups showed significantly higher levels of serum urea nitrogen and creatinine, which were even much higher in the ob/ob/I/R group than those in the ob/+/I/R group. No obvious tubular damage and TUNEL positive cells were observed in the sham groups, but severe tubular lysis, loss of brush border, sloughed debris in tubular lumen space and TUNEL-positive cells were observed in the I/R groups and were much more obvious in the ob/ob/I/R group than those in the ob/+/I/R group.Significantly increased Caspase3, Caspase9 and LC3 II protein expression and decreased p-mTOR protein expression were detected in both of the I/R groups comparing with the sham groups, these changes were more significantly in the ob/ob/I/R group than in the ob/+/I/R group. P-AMPK,P-PTEN,P-AKT,P-ERK protein were significantly down-regulated and PTEN protein was significantly up-regulated in both of the I/R groups compared with the sham groups, these changes were were much more remarkable in the ob/ob/I/R group than in the ob/+/I/R group.
Conclusion
After IRI, Mice showed impaired renal function, damaged kidney tubules and increased apoptosis and autophagy, which were significantly more obvious in the ob/ob/I/R group than in the ob/+/I/R group. The ob/ob/I/R group showed remarkably increased PTEN protein and decreased P-AMPK,P-PTEN,P-AKT,P-ERK protein than the ob/+/I/R group. All the above results suggests that leptin may participates in the pathogenesis of I/R-induced AKI by regulating autophagy via a complicated network composed of mTOR dependent pathways, as well as by regulating apoptosis.
Funding
- Government Support - Non-U.S.