Akt/mTOR expression is involved in iodinated contrast media induced renal cell apoptosis in diabetic rats

Objective To investigate molecular mechanisms of renal cell apoptosis on CIAKI in vivo, especially the involvement of Akt/mTOR signal pathways. Methods Diabetic Sprague-Dawley rats were induced by intraperitoneal injection of streptozotocin. Ten weeks later the normal and diabetic rats were administered 60% meglumine diatrizoate (DTZ) or normal saline (10 ml/kg) injection for two days continuously. 24 h after the operation, the rats were killed, stored blood samples for examining blood creatinine and kidneys for immunohistochemistry and western blotting analysis. The expression of caspase-3 in the kidney was investigated by immunohistochemistry. Meanwhile, quantitative analysis of the Bcl-2, Bax, upstream signal molecule p-Akt and p-mTOR protein expression by western blotting was used to study renal cell apoptosis on CIAKI. Results Compared with diabetic group (D group), the serum creatinine was significantly increased in diabetes+contrast media (DTZ) group (DC group) after operation [(103.89±9.01)μmol/L vs. (71.52±7.03)μmol/L, P=0.000]. The creatinine clearance rate (Ccr) was also significantly decreased in DC group after operation[(1.49±0.33)ml/min vs. (2.60±0.54)ml/min, P=0.001]. Especially in the diabetic kidney, the expression of caspase-3 was also significantly increased after intravenous injection HOCM compared with normal saline. And the expression of anti-apoptosis Bcl-2 protein was significantly decreased in DC group after the induction of DTZ, while the expression of promoting apoptosis protein Bax was significantly increased (0.90±0.13 vs. 1.50±0.16; 0.92±0.04 vs. 0.51±0.05, both P=0.000). The activity of upstream signal molecule p-Akt and p-mTOR was significantly decreased (0.46±0.08 vs. 0.68±0.07, P=0.002; 0.19±0.04 vs. 0.50±0.07, P=0.000). Conclusions The ionic high osmolality CM induce severe renal cells apoptosis in diabetic rats through activating the caspase-3 apoptotic pathway that may be mediated by upstream Akt/mTOR (inhibiting p-Akt and p-mTOR expression) signal pathways. Key words: Diabetes mellitus; Contrast induced acute kidney injury; Apoptosis; Akt/mTOR signal pathways