Effect of FTY720 on Angiotensin Ⅱ-mediated chronic kidney diseases

Objective To assess effect of fingolimod (FTY720) on functions of the kidney in rats by establishing the rat mode of angiotensin Ⅱ (Ang Ⅱ)-perfused renal injury and using the drug to intervene the rat model; and to explore action of FTY720 on renal inflammation changes and its potentially involved mechanism in the angiotensin Ⅱ-perfused rat, so as to provide a new strategy for treatment of kidney diseases. Methods Thirty-six male SPF grade Sprague-Dawley rats were randomly divided into 3 groups:(1) model group, 12 rats, i.e. Ang Ⅱ-perfused group:, Ang Ⅱ -containing osmotic micro-pump implanted subcutaneously for 28 days (Ang Ⅱ:400 ng·kg^-1·min^-1); (2) intervention group, 12 rats, i.e. Ang Ⅱ+FTY720 intervention group,:intragastrical administered with FTY720 at a concentration of 0.5 g·kg^-1·d^-1 for 28 days on the basis of the Ang Ⅱ-perfused group; (3)Control group:12 rats, intragastrical administered with the same amount of normal saline for 28 days. Twenty four hours urine samples were preserved, blood samples were collected and kidney specimens were excised and preserved on day 28 when the rats were sacrificed. Concentrations of Ang Ⅱ in blood samples and homogenized renal tissue homogenates from the rats in various groups were detected by radioimmunoassay. Urine proteins and blood biochemical parameters were tested. Renal pathological changes in rats from various groups were observed under an optical microscope and scored by Jablonski grade. The expression levels of TNF-α and IL-6 in kidney tissue were analyzed by western blot. Results (1) Ang Ⅱ increased the levels of serum creatinine and urea nitrogen in the rats from the model group. Meanwhile, in the model group, urine protein excretion increased significantly, and expression levels of inflammatory factors of TNF-α and IL-6 in the kidney tissues were elevated. (2) Compared with the model group, the renal pathological injury was significantly alleviated in the intervention group. Meanwhile, the Jablonski grades in the intervention group were significantly lower than those in the model group. Serum creatinine and urea nitrogen levels in the intervention group were significantly reduced, and urine proteins decreased notably. The levels of inflammatory factors of TNF-α and IL-6 in the kidney tissues in the intervention group were also significantly decreased, compared to model group, with statistically significant difference(P<0.05). Conclusions FTY720 can alleviate pathological damage of the kidney in rats induced by Ang Ⅱ, which may decrease urinary proteins and improve the renal function by reducing expression of inflammatory factors.