Dexmedetomidine hydrochloride up-regulates expression of hypoxia inducible factor-1α to alleviate renal ischemiareperfusion injury in diabetic rats / 南方医科大学学报

ABSTRACT

OBJECTIVE@#To verify whether dexmedetomidine hydrochloride (Dex) alleviates renal ischemia-reperfusion (IR) injury in diabetic rats by increasing the expression of hypoxia inducible factor-1 (HIF-1).@*METHODS@#A rat model of type 2 diabetes mellitus was established by high-fat diet and streptozotocin injection. The rats were subjected to daily intragastric administration of 0.05 mg/kg digoxin for 7 consecutive days and intraperitoneal injection of Dex 2 h before renal IR injury induced by ligation of the bilateral renal arteries for 60 min followed by reperfusion for 120 min. After reperfusion, blood samples were taken for detection of serum creatinine (Scr) and urea nitrogen (BUN) levels. Western blotting was used to detect the expression of HIF-1, cleaved caspase-3, Bcl-2, and Bax in the renal tissues; the expression of the HIF-1, p-eNOS, and eNOS were detected using ELISA. The percentage of apoptotic glomerular cells was assessed using TUNEL assay.@*RESULTS@#The levels of Scr, BUN, HIF-1, p-eNOS, and eNOS and the percentage of apoptotic cells in both normal and diabetic rats increased significantly after renal IR injury ( < 0.05). The expressions of Scr, BUN, p-eNOS, and eNOS decreased while HIF-1 expression increased significantly in Dex-treated rats with renal IR injury ( < 0.05). Compared with the non-diabetic rats, the diabetic rats showed more obvious increase in the expressions of Scr, BUN, p-eNOS, and eNOS following renal IR injury. In the diabetic rats with renal IR injury, Dex treatment prior to the injury significantly lowered the expressions of Scr, BUN, p-eNOS, eNOS, cleaved caspase-3, and Bax, decreased the percentage of apoptotic cells, and increased the levels of HIF-1a and Bcl-2 ( < 0.05). Digoxin treatment significantly antagonized the effects of Dex in the diabetic rats with renal IR injury by increasing the expressions of cleaved caspase-3 and Bax, promoting glomerular cell apoptosis, and decreasing renal expressions of HIF-1 and Bcl-2 ( < 0.05).@*CONCLUSIONS@#Dex alleviates renal IR injury in diabetic rats probably by inhibiting renal expression of HIF-1 and glomerular cell apoptosis.