Role of HIF-1α in renal injury induced by myocardial ischemia-reperfusion in diabetic rats: relationship with SLC7A11 / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of hypoxia-inducible factor-1α (HIF-1α) in the renal injury induced by myocardial ischemia-reperfusion (I/R) in diabetic rats and its relationship with solute carrier family7 member11 (SLC7A11).Methods:SPF-grade healthy male Sprague-Dawley rats, aged 4 weeks, weighing 100-130 g, were fed with high-fat and high-sucrose diet freely.The weight of the rats was measured once a week.After the weight of the animals reached 240 g, 1% streptozotocin (STZ)-citrate buffer 35 mg/kg was injected intraperitoneally to induce type 2 diabetes mellitus.After injection of STZ, the animals were fed with high-fat and high-sucrose diet continuously.Blood samples were collected from the tail vein for determination of blood glucose concentrations 1 week later.When random blood glucose was ≥16.7 mmol/L for 3 times, the model of type 2 diabetes mellitus was considered to be established successfully.After the model was established successfully, the animals were fed with high-fat and high-sucrose diet continuously for 6 weeks.Eighteen rats with type 2 diabetes mellitus were selected and divided into 3 groups ( n=6 each) using a random number table method: diabetic sham operation group (group DS), diabetic myocardial I/R group (group DIR) and diabetic myocardial I/R+ HIF-1α agonist DMOG group (DIR+ DMOG group). Twelve non-diabetic rats were divided into 2 groups ( n=6 each) using a random number table method: non-diabetic sham operation group (NS group) and non-diabetic myocardial I/R group (NIR group). The rat myocardial I/R injury model was established by ligating the anterior descending branch of the left coronary artery for 30 min followed by 120 min reperfusion in anesthetized rats.Blood samples were collected from the right internal carotid artery at 120 min of reperfusion for determination of the serum creatinine (Cr), urea nitrogen (BUN) and neutrophil gelatinase-associated lipocalin (NGAL) concentrations (by enzyme-linked immunosorbent assay). Renal tissues were obtained for examination of the pathological changes (by HE staining method) and for determination of the expression of HIF-1α and SLC7A11 (by Western blot). The damage to the renal tubules was scored. Results:Compared with group NS, the concentrations of serum Cr, BUN and NGAL and renal tubular damage score were significantly increased in group DS and group NIR, the expression of HIF-1α and SLC7A11 was down-regulated in group DS, and the expression of HIF-1α and SLC7A11 was up-regulated in group NIR ( P<0.05). Compared with group DS, the concentrations of serum Cr, BUN and NGAL and renal tubular damage score were significantly increased, and the expression of HIF-1α and SLC7A11 was up-regulated in group DIR ( P<0.05). Compared with group NIR, the concentrations of serum Cr, BUN and NGAL and renal tubular damage score were significantly increased, and the expression of HIF-1α and SLC7A11 was down-regulated in group DIR ( P<0.05). Compared with group DIR, the concentrations of serum Cr, BUN and NGAL and renal tubular damage score were significantly decreased, and the expression of HIF-1α and SLC7A11 was up-regulated in group DIR+ DMOG ( P<0.05). Conclusion:HIF-1α is involved in the renal injury induced by myocardial I/R, which is related to regulation of the expression of SLC7A11 in rats.