Regulation of fluvastatin on ERK1/2 and CTGF expression in cultured glomerular mesangial cells of rats induced by high glucose / 吉林大学学报(医学版)

ABSTRACT

Objective To observe the effect of fluvastatin on the activity of extracellular signal-regulated kinase(ERK)1/2,expression of connective tissue growth factor(CTGF) in glomerular mesangial cells stimulated by high glucose,and explore the pathogenic mechanism of diabetic nephropathy(DN) and its early prevention and treatment.Methods The study consisted of two parts,the first part was to repeat the existing experienment of stimulatory effect of high glucose on mesangial cells,and validated that high glucose could up-regulated the expression of CTGF through stimulating ERK,and the change was unrelated with hypertonic conditions.There were five groups①normal control group(NG);②high glucose group(HG);③mannitol group(MN);④NG+ERK inhibitor PD98059 group(NG+PD);⑤HG+ ERK inhibitor PD98059 group(HG+PD).The second part was to observe the changes of the expressions of CTGF protein and mRNA in mesangial cells at high glucose concentration before and after fluvastatin intervention.There were also five groups①normal control group(NG);②high glucose group(HG);③normal glucose and fluvastatin group(NG+F);④high glucose + fluvastatin(HG+F);⑤high glucose + fluvastatin and mevalonic acid group(HG+F+M).The activity of ERK1/2 and the expressions of CTGF protein and mRNA in cultured glomerular mesangial cells stimulated by high glucose were detected with Western blotting and RT-PCR.The amount of fibronectin(FN) in the supernatant of cells was analyzed by ELISA.Intracellular total protein level was measured by Coomassie brilliant blue method.Results The first part showed that the activity of ERK1/2 and the expression of CTGF protein in HG were more higher than those in NG(P