[Aliskiren inhibits angiotensin II/angiotensin 1-7(Ang II/Ang1-7) signal pathway in rats with diabetic nephropathy].

ABSTRACT

Objective To investigate the role of aliskiren (AL) in the angiotensinII/ angiotensin 1-7 (AngII/Ang1-7) signal pathway in renal tissue of diabetic nephropathy (DN) rats. Methods 40 male SD rats were randomly divided into 4 groups including normal group, diabetes group, AL group and valsartan (Val) group. Animal models of diabetes were induced by high fat diet combined with small dose of streptozotocin injection. Rats in AL group were administered 50 mg/(kg.d) AL by gavage, and rats in Val group were administered 30 mg/(kg.d)Val by gavage. 24-hour urine protein (24 h-UP) were observed by Coomassie blue colorimetry at 2, 4 and 6 weeks after modeling, serum creatinine was detected by automatic biochemical analyser, kidney index [kidneys mass(g)/body mass (kg)] was measured. HE and PAS staining were used to observe renal pathological changes. Immunohistochemistry was used to detect the expression of ACE2, MAS receptor, AT1R and AT2R in the kidney. Results After 6 weeks of modeling, there was no significant difference in creatinine level among groups. The levels of glucose, 24 h-UP and kidney index in diabetes group, AL group and Val group significantly increased. Compared with diabetes group, the levels of 24 h-UP and kidney index were lower in AL group and Val group. Immunohistochemistry showed that the expression of AT2R and ACE2 was lower and the expression of MAS receptor was higher in AL group than diabetes group and Val group. Compared to normal group and Val group, AT1R expression was significantly up-regulated in AL group, without significant difference between diabetes group and AL group. Conclusion AL down-regulates the expression of AT2R and ACE2, thus inhibits the AngII/ Ang1-7 signal axis and improves/alleviates the symptoms in diabetic rats.