Abstract:

Objective To investigate the effects of pretreatment with Tranilast, indoleamine 2,3-dioxygenase (IDO) high expression activator on the structure and function of mouse renal tissues with renal ischemic reperfusion injury (RIRI), and explore its possible mechanism. Methods C57BL/6 mice were randomly divided into sham operation group, RIRI group, low dose Tranilast pretreatment+RIRI group (intragastric administration of 300 mg/kg Tranilast for 3 d before model establishment) and high dose Tranilast pretreatment+RIRI group (intragastric administration of 600 mg/kg Tranilast for 3 d before model establishment). Twenty-four hours after operation, blood samples were obtained from the fossa orbitalis vascular plexus in each group, mice were sacrificed, and spleen and kidneys of both sides were obtained. Serum creatinine (SCr) and blood urea nitrogen (BUN) were measured with automatic biochemistry analyzer, the distributions of type 1 helper T lymphocyte and type 2 helper T lymphocyte (Th1/Th2) in spleen tissues of each group were determined by flow cytometry, the pathological changes of renal tissues were observed under light microscope with HE staining, the relative expression of IDO mRNA and protein in renal tissues was detected by Real-Time PCR and Western blotting respectively, serum concentrations of kynurenine and tryphtophan were measured with high performance liquid chromatography, and serum IDO activity was estimated. Results Compared with RIRI group, SCr and BUN levels and Th1/Th2 in spleen tissues in low dose Tranilast pretreatment+RIRI group and high dose Tranilast pretreatment+RIRI group were significantly lower (P＜0.01), the pathological damage in renal tissues was more moderate, the expression of IDO mRNA and protein in renal tissues and serum IDO activity were significantly higher (P＜0.01), and all the above parameters changed in a dosedependent manner (P＜0.05 or P＜0.01). Conclusion Pretreatment with Tranilast has protective effects on the structure and function of renal tissues in mice, and the mechanism may be associated with the high expression of IDO and negative immunoregulation.

Key words: Tranilast, ischemic reperfusion injury, indoleamine 2,3-dioxygenase, kidney, mouse