Expressions of apoptosis-related gene Bax, Bcl-2 and cytochrome C in renal tissue of streptozotocin-induced diabetic rats / 第二军医大学学报

ABSTRACT

Objective To observe the changes in expressions of apoptosis-promoting gene Bax, apoptosis-inhibiting gene Bcl-2, and cytochrome C in the renal tissue of diabetic rats. Methods Twenty-four male Sprague-Dawley rats were randomly divided into 2 groups (n=12) normal control group and diabetic group. Diabetic models were induced by single intraperitoneal injection of 2% streptozotocin (dissolved in pH 4. 4,0. 1 mol/L citric acid sodium buffer, 65 mg/kg). Normal control group was only injected with same volume of folie buffer. Animals were sacrificed at the 4th and 12th week, and body mass, 24-hour urine protein, blood glucose, blood urine nitrogen and serum creatinine were determined. The changes of the renal morphology were observed by H-E staining. Immunohistochemical method was used to investigate the expressions of Bax, Bcl-2 and cytochrome C protein. The apoptosis of renal cortex cells was determined by TUNEL method. Results Compared with normal control group, the 24-hour urine protein, blood glucose, blood urine nitrogen and serum creatinine were significantly increased in the diabetic group (P<0. 05, P<0. 01). The size of glomerulus was increased in diabetic rats during the 4th week; hyperplasia of renal glomerulus mesangial matrix, glomerular sclerosis, and vacuolar degeneration in renal tubular epithelial cells were observed during the 12th week. With disease progression in the diabetic group, the expressions of Bax and cytochrome C were increased and the expression of Bcl-2 was decreased. Apoptosis tests showed increased apoptotic cells in the 4th week, mostly in both the distant tubular epithelial cells; in the 12th week, apoptotic cells were seen in both the distant tubular and proximal tubules. Conclusion Renal expression of Bax and cytochrome C gradually increases with the progression of diabetes, inducing apoptosis of more cells and leading to renal dysfunction, which may partly contribute to the diabetic nephropathy in diabetic rats.