The Effect And Mechanism On Regeneration And Repair In Renal Tubular Epithelial Cell After Injury By The Inhibitory Proliferation Effect Of ACEI And ARB

Objective: To study the effect of fosinopril (Fos) and valsartan (Val) on regenerationand repair of renal tubular epithelial cells after injury, and to explore the function andmechanism of proliferation inhibition of angiotensin-converting enzyme inhibitors(ACEI) and angiotensin type1receptor antagonist(ARB) induced acute kidney injury.Method: HK-2cells were cultured in DMEM/12medium (containing5%fetal bovineserum), the anoxia-reoxygenation cells model was established. Fos (10μmol/L), Val(10μ mol/L) or Fos and Val intervened cells48h after hypoxia reoxygenation, Cells ineach group were observed under an inverted microscope and photographed, cellproliferation was detected by MTS colorimetry and Brud incorporation, concentrationof (angiotensinII)AngII in cell supernatant was detected by Elasa,(angiotensin-converting enzyme)ACE,(angiotensin-converting enzyme2)ACE2,(angiotensintype1receptor antagonist)AT1R, and (angiotensin type1receptor antagonist)AT2RmRNA expression was detected by real-time PCR, ACE2, AT1R, and AT2R proteinexpression was detected by western bloting;In additon, AT2R antagonist PD123319（10μmol/L）and Val（10μmol/L） intervened the cells48h after hypoxiareoxygenation, cells in each group were observed and photographed ibid, cellproliferation was only detected by MTS colorimetry, AngII concentration in cellsupernatant was detected in same method as above. AT1R and AT2R Mas1proteinexpression was detected by western bloting.Result:Part I:(1) HK-2cells hypoxia3h,24h reoxygenation,cell viability mostsignificantly decreased (P<0.05),cytotoxicity increase larestly(P<0.05),angiotensinIItype2receptor expression was increased (P<0.05);(2) To compared with HRI, The cells proliferation activity of HRI+Fos group was decreased (P<0.05), cells BrdUincorporation rate was decreased (P<0.05), ACE mRNA was down regulated(P<0.05), the AngII concentration was decreased in cell supernatant(P<0.05), andhave significant positive correlation with the cell proliferation activity;(3) Tocompared with HRI group, cells proliferation activities of HRI+Val group was notinhibited (P>0.05),cells BrdU incorporation was also no difference (P>0.05), AT1Rwas down regulated (P<0.05);(4) To Compared with the HRI group, cellsproliferative activity of HRI+the PD123319group was inhibited (P <0.05), andangiotensinII type2receptor expression was reduced (P <0.05).Conclusion:(1) These results suggest that the HK-2cells after hypoxiareoxygenation can be simulated tubular epithelial cell damage.(2) ACEI could beinhibit the regeneration and repair of renal tubular epithelial cell after injury;(3) ARBhave no significantly inhibit the regeneration and repair of renal tubular epithelial cellafter injury;(4) PD123319inhibit the regeneration and repair of renal tubularepithelial cell after injury...