Effect Of Astragaloside Ⅳ On Rats With Chronic Anti-thy1Nephritis

Background and ObjectivesMesangial cell proliferation is the major pathological feature of immune mediated glomerular disease. Sustained cell proliferation and matrix expansion can lead to progressive irreversible glomerulosclerosis and can ultimately lead to end-stage renal disease (ESRD) which threats to public health seriously. Mesangial proliferative glomerulonephritis (MsPGN), which includes IgA nephropathy and non-IgA mesangial proliferative lesions, is the most common cause of glomerular disaease. Analysis of the data of13,519renal biopsy specimens of patients showed that MsPGN constituted70.88%of the primary glomerulonephritis (GN)(IgA nephropathy was45.26%, while non-IgA mesangial proliferative lesions were25.62%). The analysis also revealed that systemic lupus erythrematosus (54.3%), the most prevalent etiology of secondary GN, is also belong to the MsPGN in pathology. MsPGN is characterized by diffuse mesangial cells proliferation and mesangial matrix expansion in different degree. Therefore, the inhibition of membrane cell proliferation is an important treatment strategy of MsPGN, and looking for suppression of mesangial cell proliferation drugs would have important clinical significance.In this study, we aimed to assess the benefits of Astragalus in treating chronic glomerulonephritis in any age group and then made use of rats with chronic anti-thy1nephritis (mesangial proliferative glomerulonephritis) to determine whether AS-â…£ has any effects on the nephritis and investigated the mechanisms of this action.MethodsFor clinical evidence-based aspects, We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, CBMdisc, CNKI, VIP database, The Chinese clinical test registration center (ChiCTR) electronic database and combined with manual retrieval. All randomized controlled trial (RCTs) or the first period of randomised crossover studies assessing the use of Astragalus in treating chronic glomerulonephritis were included. There was no language restriction. Two authors assessed study quality and extracted data independently. Revman5.1.6for meta-analysis was used. For experimental studis,24wistar rats were divided into three groups:a sham operation group, a Thy-1rats group, and a Thy-1with AS-IV treatment group. Proteinuria and pathological changes were evaluated after treatment with AS-IV for3months. In vitro study, effect of AS-â…£ on mesangial cells proliferation were determined. MEK, phosphorylation of MEK1(p-MEK), ERK1/2, phosphorylation of ERK1/2(p-ERK1/2), the key molecules of ERK/MAPK signaling pathway, CyclinDl, CDK4, the key rgulators of cell cycle, and PCNA, a proliferation marker, in kidney and in mesangial cells were determined.ResultsFor clinical evidence-based aspects, The four adopted researches are parallel design with the control groups (n=298). Trials with at least30days for therapy and follow-up should been used. Meta analysis of Astragalus versus control-up for chronic glomerulonephritis decrease24h proteinuria and increase the total effect rate of therapy. There are no difference between injection combining with foundation treatment and foundation treatment groups. With the use of GRADEprofiler software recommended by the Cochrane Collaboration to evaluate evidences quality, the strength of evidence was very low. For experimental studis, AS-IV significantly decreased the levels of24h proteinuria, Urine protein/Urine creatinine ratio, total cholesterol and triglyceride; dramatically inhibitedalleviated proliferation of mesangial cells; and reduced the expressions of p-MEK, p-ERKl/2, CyclinDl, CDK4, and PCNA in kidney and in mesangial cells.ConelusionsFor clinical evidence-based aspects, Astragalus may work in chronic glomerulonephritis. It could decrease24h proteinuria and increase the total effect rate of therapy. As the studies belong to lower qualities and had not time enough in treatment, the strength of evidence is lower. So big sample RCTs and multiply-center should be used to assess the effect of therapy in person with chronic glomerulus disease. For experimental studis, AS-IV could inhibit renal mesangial cells proliferation and improve renal damage;this might be associated with inhibition of ERK/MAPK pathway to transactivate target genes such as cyclin Dl and stimulate G1to S phase progression in cell cycle.