Effect of atorvastatin on NF-κB in peripheral blood mononuclear cells and renal tissues in diabetic rats
Li Lon
Abstract
Li Lon
Abstract
Objective To investigate the protective effect of atorvastatin on diabetic nephropathy(DN)and its mechanisms.Methods The rat diabetic model was made by the intra-peritoneal injection of streptozocin.The rats were divided into three groups of normal control,diabetes,diabetes treated with atorvastatin(2 mg·kg-1·d-1)by gavage.Activity of nuclear factor kappa B(NF-κB)in peripheral blood mononuclear cells(PBMC)was analyzed by Enzyme-linked Immunosorbent Assay(ELISA).Expressions of NF-κB,MCP-1 and fibronectin(FN)in renal tissue were measured by immunohisto-chemical stain,24-hour urinary protein,and plasma creatinine(Cr)were measured.Results NF-κB activities in PBMC and renal tissues(RT)in diabetic rats were significantly higher than those in normal rats(2.45±0.31 vs 0.37±0.15,as OD value in PBMC P0.01;9.842±1.653 vs 1.116±0.467 as NF-κB positive cell number in RT,P0.01).While compared with diabetic rats,atorvastatin treatment significantly inhibited activation of NF-κB(0.58±0.06 vs 2.45±0.31,P0.05 in PBMC;4.158±1.552 vs 9.842±1.653,P0.05 in RT),reduced expression of FN,decreased urine protein excretion,ameliorated mononuclear infiltration,improved renal function and pathological changes of renal histology.Conclusions These results suggest the activated NF-κB plays a pathogenic role for diabetic nephropathy.Atorvastatin treatment slows down the development of DN.The protective effect of atorvastatin on DN appears to be mediated through the inhibition of activation of NF-κB.
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Objective To investigate the protective effect of atorvastatin on diabetic nephropathy(DN)and its mechanisms.Methods The rat diabetic model was made by the intra-peritoneal injection of streptozocin.The rats were divided into three groups of normal control,diabetes,diabetes treated with atorvastatin(2 mg·kg-1·d-1)by gavage.Activity of nuclear factor kappa B(NF-κB)in peripheral blood mononuclear cells(PBMC)was analyzed by Enzyme-linked Immunosorbent Assay(ELISA).Expressions of NF-κB,MCP-1 and fibronectin(FN)in renal tissue were measured by immunohisto-chemical stain,24-hour urinary protein,and plasma creatinine(Cr)were measured.Results NF-κB activities in PBMC and renal tissues(RT)in diabetic rats were significantly higher than those in normal rats(2.45±0.31 vs 0.37±0.15,as OD value in PBMC P0.01;9.842±1.653 vs 1.116±0.467 as NF-κB positive cell number in RT,P0.01).While compared with diabetic rats,atorvastatin treatment significantly inhibited activation of NF-κB(0.58±0.06 vs 2.45±0.31,P0.05 in PBMC;4.158±1.552 vs 9.842±1.653,P0.05 in RT),reduced expression of FN,decreased urine protein excretion,ameliorated mononuclear infiltration,improved renal function and pathological changes of renal histology.Conclusions These results suggest the activated NF-κB plays a pathogenic role for diabetic nephropathy.Atorvastatin treatment slows down the development of DN.The protective effect of atorvastatin on DN appears to be mediated through the inhibition of activation of NF-κB.
Key concepts: Diabetic nephropathy, Peripheral blood mononuclear cell, Atorvastatin, Internal medicine, Endocrinology, Diabetes mellitus, Medicine, Mononuclear cell infiltration