ABSTRACT
Aim To observe the effects of tetrahydro-biopterin ( BH4 ) on nitric oxide ( NO ) production in the kidney of type 2 diabetic nephropathy ( DN) mice, and to find a new target for the treatment of type 2 DN. Methods The 12 week-old db/db mice developed in-to DN phase were divided into 2 groups:DAHP group, subjected to intraperitoneal injection of 150 mg·kg-1 DAHP (n=8);DN group, subjected to intraperitone-al injection of same dose of normal saline containing 5% DMSO ( n = 6 ) . The age-matched db/m mice ( NS group) were subjected to intraperitoneal injection of same dose of normal saline containing 5% DMSO ( n =6 ) . Three groups of mice were treated for 7 days. Then the fasting blood-glucose, serum creatinine, u-rine protein and activity of iNOS were determined by chemical colorimetry. And the iNOS protein in renal cortex was determined by immunohistochemisty and western blot, respectively. BH4 was measured by HPLC method. NO level was determined by Griess method. Results The levels of fasting blood-glucose, serum creatinine, 24h urine volume, 24h urine pro-tein, BH4 , iNOS and NO in DN group were signifi-cantly higher than those in NS group;The levels of ser-um creatinine, urine volume, urine protein, BH4 , iN-OS and NO in DAHP group were significantly lower than those in DN group. Conclusion In the kidney of type 2 DN mice, the increased BH4 contributes to over-production of NO by the increased iNOS expression, and resultes in the increase of urine volume and urine protein.