대한신장학회

논문분류	춘계학술대회 초록집
제목	SGLT2 Inhibitor Attenuates Ischemia Reperfusion Renal Injury
저자	Yoon Kyung Chang1, Hyun Su Choi1, Jin Young Jeong2, Sarah Chung2, Dae Eun Choi2, Ki Ryang Na2, Kang Wook Lee2
출판정보	2015; 2015(1):
키워드	SLGT2 억제,허혈재관류신손상,HIF1
초록	Introduction: SGLT2 inhibitor, dapagliflozin were developed for diabetes control. it wastes the glucose to urine. Although SGLT2 KO mice study showed no reduction of inflammation markers in type 1 DM mice model, some studies showed SGLT2 inhibition have renal protection (reduce hyperfiltration and tubular oxidative stress) in Type1 DM. We evaluate whether SGLT2 inhibitor reduces the renal damage via ischemia reperfusion (IR). Also, we investigate the associating molecular pathway. Methods: in vitro, IR was simulated by mineral oil in HK-2 cells. Cell survival, apoptosis signal pathway, reactive oxygen species (ROS) generation, HIF1, ERK, AMPK, PGC1 alpha were evaluated in control and IR HK-2 cell with or without SGLT2 inhibitor. In vivo 10 weeks C57BL/6 mice were divided into 4 groups; vehicle (n=5) and dapagliflozin (10 mg/kg PO 4hr and 1hr before operation) treated sham group (n=5), vehicle n=7) and dapagliflozin (n=7) with IR (reperfusion 27 minutes after clamping of both renal artery and vein) renal injury. Kidneys and blood were harvested 24hr after IR injury. We performed real time RT-PCR, western blot and immunohistochemistry for molecular study and H&E stain and PAS stain for histologic examination. Results: Dapagliflozin treatment significantly increase survival of IR HK-2 cells. Dapagliflozin treatment increase the level of HIF1 in IR HK-2 cells. Also it decrease the Bax/Bcl2 ratio and 8-OH deoxyguanosine generation. in vivo, The levels of BUN and serum creatinine in IR renal injury with dapagliflozin treated mice were significantly lower than that of vehicle with IR renal injured mice (p<0.05). In microscopy, dapagliflozin significantly reduced renal tubular epithelial cell necrosis and detachment. Dapagliflozin significantly increased the expression of HIF1 in IR kidney. Dapagliflozin significantly reduced 8-OH deoxyguanosine positive and TUNEL positive cells in IR kidney. Also it significantly decreased the level of Bax/Bcl-2 ratio and phosphorylated caspase -3. Conclusion: In conclusion, dapagliflozin significantly increases HIF1 in IR injured kidney. Also it attenuates ischemia reperfusion renal injury.
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