ABSTRACT
Objective To explore the reversibility of early stage tubular interstitial injury as well as the timing of reparation through the pig relief of unilateral ureteral obstruction (R-UUO) model.Methods Eight three-month-old female Guangxi BA-MA mini pigs were selected for the construction of R-UUO models.Five time points were set which were UUO 0 day,UUO 3 days,R-UUO 7 days,R-UUO 14 days,and R-UUO 21 days.Renal function,histological structure,and protein expressions of α-smooth muscle actin (α-SMA),vimentin and E-cadherin were evaluated at different time points.Results After 3 days of UUO,compared with UUO 0 day,serum creatinine levels were increased obviously and the kidney tissues presented varying degrees of damage.The expressions of α-SMA and vimentin were increased and E-cadherin expression was decreased (P ＜ 0.05).Following R-UUO after 3 days of UUO,compared to UUO,serum creatinine levels were significantly decreased.Renal pathological tissue damage was repaired.The expressions of α-SMA and vimentin were decreased and E -cadherin expression was increased (P ＜ 0.05).Conclusions The pig R-UUO animal model may provide a good platform to study the kidney injury and repair.The tubular injury may be fully reversed and repaired when removing the pathogenic factors if the renal tubular injury was at an earlier stage.
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 groups:①normal 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 groups:①normal 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