Effects of angiotensin converting enzyme inhibitor on expression of transforming growth factor β1 and β1-integrin in glomerular mesangial cells induced by lipopolysacchatide / 国际儿科学杂志

ABSTRACT

Objective To observe the effects of one kind of angiotensin converting enzyme inhibitor (ACE1) drugs fosinopril (FOS) on transforming growth factor β1 (TGF-β1)and β1- integrin( Itg-31 ) expression in rat glomerular mesangial cells (GMC)induced by lipopolysacchatide (LPS).Methods We established the cultured glomerular mesangial cells of rat in vitro and passages 3 ～ 10 of cells were used in the experiment after identification.The experiment included the following groupsControl group,LPS induced group (LPS group) and FOS intervened group.According to the different concentrations of FOS,FOS intervened group was divided into high,middle and low dose FOS groups,which were FOS1 group,FOS2 group and FOS3 group respectively.The changes of TGF-β1 protein secretion was detected by the enzyme-linked immunosorbent-assay; The changes of TGF-β1 and Itg-β1 mRNA expression was detected by quantitative real-time RT-PCR.Results (1) TGF-β1protein secretion in rat GMC at 6h,12h,24h three time pointsThey were 958.55 ± 34.67 ( ng/L),1052.05 ±48.59( ng/L),1166.06 + 35.39 (ng/L) respectively in Control group.They were 1342.12 + 39.87 ( ng/L),1432.31 + 39.33 (ng/L) and 1 537.77 + 43.79 (ng/L) respectively in LPS group,which were higher significantly than those in Control group ( all P ＜ 0.01 ).They were 779.58 ± 48.64 ( ng/L),878.33 ± 29.50 (ng/L) and 962.57 ±31.94( ng/L) in FOS1 group,989.311±73.56(ng/L),1073.29±66.89(ng/L) and 1210.75 ±61.68(ng/L) in FOS2 group,1 253.78 ±45.32( ng/L),1 348.18 ±45.81 (ng/L) and 1450.06 ±46.24( ng/L) in FOS3 group respectively,which were lower significantly in all FOS intervened groups than that in LPS group (all P＜O.01).(2)TGF-β1 mRNA expressions in rat GMC at6h,12h,24h three time points were higher significantly than that in Control group.TGF-β1 mRNA expressions were lower significantly in all FOS intervened groups than that in LPS group.( 3 ) Itg-β1 mRNA expressiones in rat GMC at 6h,12h,24h three time points were higher significantly than that in Control group.Itg-β1 expressions were lower significantly in all FOS intervened groups than that in LPS group.Conclusions LPS can induce the increase of TGF-β1 secretion and mRNA expression.FOS can inhibit the TGF-β1 secrection and mRNA expession in GMC as dose-dependent manner,at the same time down regulated the Itg-β1 mRNA expression iuduced by LPS.All above supply the theoretical evidence for the renal protection of FOS by non-hemodynamics mechanism.