| Objective:research the therapeutic effect of HGF in DN in different phases by measuring the expression of TGF-β1mRNA,CTGFmRNA and c-met mRNA and the changes of parameters after injecting intraperitoneally hHGF in rats of DN.Methods:Seventy male Wistar rats after born 4 to 8 weeks were divided randomly into three groups.There were twenty four in normal control group(NC),twenty four in diabetic nephropathy(DN) and twelve in therapy(HGF group).The subjects in DM group and HGF group were injected intraperitoneally with low dose streptozotocin(STZ,30mg/kg) after high calorie diet given for two months,while the ones in NC group were injected intraperitoneally with the similar dose of citrate buffer.Two months,three months,six months and seven months after administration,rats were placed in metabolic cages to collect 24-h urine specimens to measure 24-hour urinary protein.The six Wistar rats in HGF group were injected hHGF (500ug/kg/day) for one month in two month and six month after injected STZ,and then were respectively killed.There were six rats in NC group and DN group after administration two months,three months,six months and seven months respectively killed.The right kidney samples were used to analyse morphologically and the left kidney samples were used to measure the expression of TGF-β1mRNA,CTGFmRNA and c-metmRNA by reverse transcription polymerase chain reaction(RT-PCR).We compare these data between the three groups and among the different stages with analysis of variance.Result:There was difference in the level of fast blood glucose between HGF and DN group from NC group after high calorie diet given for two months(p＜0.01).The difference was significant after injected intraperitoneally with STZ and the level of FBG was increasing with the progression of DM,then sustained at the level of 16.5-16.8mmol/L.The change was similar to type 2 diabetes mellitus.The groups of HGF and DN were charactered by microalbuminuria and glomerular hypertrophy(higher kidney weight),whereas GBM and ECM were thicker lightly.Compared with the NC group,the expression of TGF-β1mRNA and CTGFmRNA were not increased obviously,but the expression of c-metmRNA was increased obviously(p＜0.05). Diabetic nephropathy was characterized by progressive albuminuria,pathologic findings were mesangial expansion,glomerulosclerosis,GBM and ECM were thither obviously,similar to human overt DN,whereas the expressions of TGF-β1mRNA and CTGFmRNA were up-regulated obviously and the expression of c-met mRNA was down-regulated obviously after injected STZ six months in DN group.Compared with DN group in month three,the albuminuria protein was not increased or decreased,GBM was not thicker,ECM was not accumulated,the expression of c-met mRNA was up-regulated and the expressions of TGF-β1mRNA and CTGFmRNA were down-regulated in HGF group injected HGF for one month after injected STZ two month.Compared with DN group in month six and seven,the albuminuria protein was decreased,GBM was thinner,ECM was degadated,the expression of c-met mRNA was up-regulated and the expressions of TGF-β1mRNA and CTGFmRNA were down-regulated in HGF group injected HGF for one month after injected STZ six month.Conclusion:HGF can inhibit the progression of DN in early stage.HGF can decrease urine albumine,make GBM thinner and degrade ECM by upregulating the expression of c-met mRNA and downregulating the expression of TGF-β1mRNA and CTGFmRNA in overt DN,so HGF can revert the progression of overt DN.
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