The Effects Of RhALR On Chronic Renal Failure With 5/6 Renal Nephrectomized Rats

Objective: In recent years, recombinant human augmenter of liver regeneration (rhALR) studies were focused on the liver.It can promote liver regeneration, liver fibrosis, inhibition of NK cell activity and so on Its mRNA in testis, liver, kidney, thymus and other organs were expressed, which shows the diversity of biological functions . It was found rhALR can contribute to the degradation of extracellular matrix, reducing the damage of liver cells and promote the recovery of liver cell injury. It is confirmed that rhALR not only involved in nephritis pathological process directly or indirectly in domestic and foreign research, but also stimulated tubular epithelial cell DNA synthesis in acute renal tubular damage.But it is still lack of chronic renal failure. The purpose of this project is through exogenous administration of recombinant augmenter of liver regeneration, understanding of exogenous administration of recombinant augmenter of liver regeneration for the protective effect of chronic renal failure, for clinical treatment provide a new way, through observation and chronic renal failure with a clear Correlation factors, protein changes.Chronic renal failure(CRF),as a progressive injury of kidney and worsening of renal function ,which is attributed to kinds of etiology,has posed great threats to patients. Fibrosis can be the main represent on renal pathological examination.Its pathological changes are glomerular sclerosis (GS) and renal interstitial fibrosis, which recognized as consequences of the tissue repair against gradually chronic injury.GS is characrerized by the progressive accumulation of extracellular matrix (ECM) components. Imbalance between remodeling of synthesis and degradation of ECM leads to over-accumulation of extracellular matrix(ECM) and precedes the development of glomerular sclerosis. Research shows that the platelet growth factor (PDGF) is secreted by platelets, monocyte macrophages, mesangial cells (GMCs) and renal tubular epithelial cells. Its family include PDGF - AA, BB, CC and DD, PDGF - BB is most important. The main physiological role is to promote DNA synthesis by mononuclear macrophages and intrinsic renal cells in excessive secretion of GMCs by promoting proliferation and secretion of extracellular matrix (ECM) increased, and transforming growth factor-β(TGF-β) play Synergies and other channels, resulting in the occurrence of GS.In renal tubular epithelial - mesenchymal cells transition process, renal tubular epithelial cells gradually losing their original form, and show fibroblasts features, Such as smooth muscle actin (а-SMA) expression is increased in renal tubular epithelial to mesenchymal cell migration,Ⅲcollagen secretion, excessive accumulation of extracellular matrix, thus renal interstitial fibrosisThis study attempts to investigate the effects of rhALR on PDGF - BB,а- SMA and collagenⅢwith 5/6 Nephrectomy Rats,finally stepping down the progression of GS.Methods:Sixty healthy male SD rats were randomly divided into three groups:sham operation group(SO,n=20),CRF model group without treatment (C,n=20) and CRF model group treated with rhALR (rhALR,n=20).The SO group was subjected to a sham operation while the C group and rhALR group gained 5/6 nephrectomize.All rats were kept in a temperature-even and humidity-controlled room for 12weeks,eating and drinking freely.12 weeks later,the model of CRF were successfully established.The rats in group rhALR received a single intraperitoneal injection of rhALR at a dose of 200ug/kg/d,once daily by one week.At the end of the study,the rats were killed,and their kidney were collected for histological and molecular biology examination.Renal tissues stained with HE and Masson were observed of changes in glomerular pathology in ordinary light microscope.The expression of PDGF - BB,а- SMA and Col-Ⅲwere measured by immunocytochemistry, The expression of PDGF - BB,а- SMA were measured by Western blot. The results were semiquantitatively analyzed with an image-processing system. All the data were analysed by SPSS13.0 statistics software,P value<0.05 was considered to have statistical significance.Result:Renal pathology: In group C, light microscopy showed glomerular compensatory hypertrophy, proliferation of glomerulus mesangial cells (GMCs) , increased of the matrix,capillary collapse, focal segmental sclerosis, inflammatory cell infiltration and fibroplasia occured in renal interstitium. Immunohistochemistry and Western blot :Expression of PDGF-BB protein, a-SMA, collagenⅢwere increased in group rhALR and group c compared with group so. which issignificantly reduced in group rhALR compared with group c. To suggest: rhALR has a protective effect for chronic renal failure.Conclusions:The rhALR acts as a factor contributing to reduce renal interstitial fibrosis by reducing PDGF-BB in the expression of chronic renal failure and kidney mesangial cell proliferation and reduce the secretion of extracellular matrix (ECM), decreased expression of smooth muscle actin (а-SMA), Thereby inhibiting the secretion of collagen typeⅢ, reduce excessive accumulation of extracellular matrix. rhALR has a protective effect of chronic renal failure.