Diabetic Rat Glomerular Mesangial Cells Of Ctgf, The Ecm Expression Changes And The Losartan Intervention Effect

Objective: To explore the actions of connective tissue growth factor (CTGF)and extracellular matrix(ECM) expression on glomeruli of diabetic rat in progression of diabetic nephropathy,and the intervention effects of Losartan, an angiotensin Ⅱreceptor antagonist(ARA).Methods: To establish diabetic model of Wistar rat induced by intraperitoneal injection of Streptozotocin(STZ),and to intervene them by application of Losartan, an angiotensin receptor antagonist. Expression of CTGFmRNA in glomeruli were analysed by in situ hybridization technique.Expression of CTGF, transforming growth factor-β(TGF-β),hepatocyte growth factor(HGF),α-smooth muscle actin(α-SMA), CD14+, Fibronectin(Fn), Laminin(Ln), Collagen type Ⅳ(Col-Ⅳ), Matrix metalloproteinase-9(MMPs), tissue inhibitor of metalloproteinase-1(TIMP-1) in glomeruli of each group were analysed by immunohistochemistry technique.Results:(1)Expression of CTGFmRNA,CTGF,TGF-β in glomeruli of diabetic model group were higher significantly than normal control(p<0.01), and expression of HGF in glomeruli of diabetic model group were lower significantly than normal control(p<0.05). There are significant positive interrelationship between expression of CTGF and TGF-β, urinary protein excretion of 24h,glomerular volume(GV); and significant negative interrelationship were showed between expression of CTGF and HGF. Above index in Losartan intervention group were improved significantly compared to diabetic model group, but still can not restore to the level of normal control group(p<0.05). (2)Expression of α-SMA and CD14+ in glomeruli of diabetic model group were higher significantly than normal control(p<0.01); There are significant positive interrelationship between expression of CTGF andα-SMA and CD14+. Above index in Losartan intervention group were improved significantly compared to diabetic model group, but still can not restore to the level of normal control group(p<0.05). (3) Expression of Fn,Ln and Col Ⅳ in glomeruli of diabetic model group were higher significantly than normal control(p<0.01); There are significant up-and-down relationship of same-direction between expression of CTGF and Fn,Ln,Col Ⅳ. Expression of CTGF and Fn,Ln,Col Ⅳ in Losartan intervention group were improved significantly compared to diabetic model group,but still can not restore to the level of normal control group(p<0.05). (4)Expression of MMP-9 in glomeruli of diabetic model group were lower significantly than normal control(p<0.01),and expression of TIMP-1 in glomeruli of diabetic model group were higher significantly than normal control(p<0.05). There are significant up-and-down relationship of negative-direction between MMP-9/TIMP-1 ratio and expression of CTGF. MMP-9/TIMP-1 ratio in Losartan intervention group were improved significantly compared to diabetic model group,but still can not restore to the level of normal control group(p<0.05).Conclusion (1)Expression of CTGF,TGF-β were up-regulated and expression of HGF were down-regulated in glomeruli of diabetic rat, meanwhile mean glomeruli volume enlarged, urinary protein excretion of 24h increased. Intervention of Losartan can improve the abnormal expression of CTGF,TGF-β and HGF partly at least, improve urinary protein excretion of 24h and mean glomeruli volume. (2)Phenotype transformation of mesangial cells and infiltration of macrophage cells existed obviously in glomeruli of diabetic rat, therefore these can exist close relationship to expression of CTGF. Losartan can decrease the phenotype transformation of mesangial cells and infiltration of macrophage cells partly. (3)Expression of ECM increased in glomeruli of diabetic rat. Close relationship between expression of ECM and CTGF were showed.Losartan can improve partly the expression levels of ECM and CTGF. It can benefit to delay the progression of diabetic nephropathy. (4)Expression of MMP-9 decreased,expression of TIMP-1 increased and MMP-9/TIMP-1 ratio decreased in glomeruli of diabetic rat.Losartan can improve partly the abnormali...