Changes of angiotensin converting enzyme 2 in the occurrence and development of diabetic renal injury in rat / 生理学报

ABSTRACT

This project was designed to investigate the role of angiotensin converting enzyme 2 (ACE2) in the diabetic renal injury by observing the expression of ACE2 in the kidney and the level of angiotensin II (AngII) in the circulatory system and kidney tissue of rats with diabetes. SD rats were randomly divided into control group and diabetes group. Diabetic nephropathy model was established by i.p. injection of streptozotocin (STZ). The rats were sacrificed separately on the 15th or 30th day after STZ injection. Biochemical parameters including blood glucose and renal function were examined. The expression of ACE2 in the kidney was detected by real-time PCR and Western blot. The contents of AngII in plasma and kidney were detected by radioimmunoassay. The results are as follows (1) 48-72 h after STZ injection, the rats showed polyuria, polydipsia and their activity reduced. (2) Blood glucose levels were 4.9-6.5 mmol/L in the control rats, 14.0-17.5 mmol/L in the diabetes group rats on the 15th day, and higher than 24 mmol/L in the diabetes group rats on the 30th day; (3) There was a significant increase of urine glucose level (P < 0.05), and a slight but not significant increase of urine protein level (P > 0.05) in the diabetes group on the 15th day; On the 30th day, the levels of urine glucose and urine protein were significantly higher than those in the control group (P < 0.01); (4) Compared with the control group, the expression of ACE2 mRNA was slightly increased (P > 0.05), and the expression of ACE2 protein was significantly increased (P < 0.05) in the rats of diabetic model group on the 15th day; however, on the 30th day, ACE2 mRNA expression in the rats of diabetic model group was significantly lower than the control group (P < 0.05), and the expression of ACE2 protein was slightly lower than the control group (P = 0.0718). (5) Compared with the control group, the levels of AngII in plasma and kidney of the diabetic rats increased slightly on the 15th day (P > 0.05); while the AngII levels in diabetic model group rats were significantly higher (P < 0.05) than that in control rats on the 30th day. These results suggest that ACE2 plays a positive role in the protection against the pathogenesis of early renal damage. ACE2 expression is reduced gradually with the deepened degree of diabetic kidney damage, leading to the accumulation of AngII in the kidney, thereby increasing the renal injury.