ABSTRACT
Studies showed that the use of cyclic adenosine monophosphate (cAMP) substitutes or intracellular cAMP activators increased intracellular cAMP level,causing anti-inflammatory effects.This study was to investigate the effects of pretreatment with meglumine cyclic adenylate (MCA),a compound of meglumine and cAMP,on systemic inflammation induced by lipopolysaccharide (LPS) in rats.Eighteen adult male Sprague-Dawley rats were randomly divided into 3 groups (n=6 each):control group (NS group),LPS group (LPS group) and LPS with MCA pretreatment group (MCA group).Systemic inflammation was induced with LPS 10 mg/kg injected via the femoral vein in LPS and MCA groups.In MCA group,MCA 2 mg/kg was injected via the femoral vein 20 min before LPS injection,and the equal volume of normal saline was given in NS and LPS groups at the same time.Three hours after LPS injection,the blood samples were taken from the abdominal aorta for determination of plasma concentrations of TNF-α,IL-1,IL-6,IL-10,cAMP by ELISA and NF-r Bp65 expression by Western blotting.The experimental results showed that inflammatory and antiinflammatory indices were increased in LPS group compared to NS group;inflammatory indices were declined and anti-inflammatory indices were increased in MCA group relative to LPS group.Our study suggested that MCA pretreatment may attenuate LPS-induced systemic inflammation.
ABSTRACT
In order to evaluate the effectiveness of everolimus vs.rapamycin in the treatment of diabetic nephropathy,8-week old diabetic (db/db) mice received everolimus (2 mg/kg every day) or rapamycin (2 mg/kg every day) for 4 weeks or 12 weeks respectively.Blood and 24-h urine samples were collected for biochemical tests.One kidney from each mouse was homogenized for protein analysis and the other was removed for histological analysis.The expression levels of transforming growth factor-β1 (TGF-βl)and phospho-p70s6k were detected by using ELISA and Western blot,respectively in the renal tissue as well as in mesengial cell culture samples.Everolimus was significantly more effective than rapamycin in improving indexes of renal function and glomerular hypertrophy,and in decreasing accumulation and expansion of the extracellular matrix.However,everolimus inhibited TGF-β1 secretion and p70s6k phosphorylation induced by high glucose in vitro less efficiently than rapamycin at the same dose.Everolimus was more effective than rapamycin in preventing diabetic nephropathy in vivo,which may be contributed to the fact that everolimus has better bioavailability and a higher oral absorptionrate.