| BackgroundIgA nephropathy(IgAN)is a group of primary glomerular diseases characterized by diffuse and widespread deposition of poly IgA or IgA in the glomerular mesangial area.It is one of the most common primary glomerular disease.Howere,the pathogenesis of IgA nephropathy is still not completely clear,and we have seldom good specific treatment methods on IgA nephropathy.Our studies on Shenbingerhao prescription show that it has a good therapeutic effect on IgA nephropathy,but the mechanism of this is not yet clear.ObjectiveTo clarify the intervention effect of Shenbingerhao prescription on rats with IgA nephropathy,and to investige the changes of serum metabonomics before and after Shenbingerhao prescription intervention in IgA nephropathy.MethodForty 4-week-old male Sprague-Dawley rats were randomly divided into five groups:normal group,model group,Shenbingerhao prescription high-dose,middle-dose and low-dose groups,each group has 8 rats.The model group and the Shenbingerhao prescription group establish the IgA nephropathy model by the following method:Bovine serum albumin(BSA)was intragastrically administered 600mg/kg every other day,and carbon tetrachloride(CC14,0.1ml)+ castor oil(0.5ml)was injected subcutaneously once every week,and lipopolysaccharide(LPS)was caudal vein injected 0.25 mg/kg on weeks 7,10,and 13 week.The whole process lasted 14 weeks.Starting from the 15th week,the Shenbingerhao prescription group was treated with high-,medium-,and low-dose gavage Shenbingerhao prescription for 6 weeks,and urine was collected for 24 hours every week.After the completion of the experiment,the kidney and liver were taken for histopathological examination and serum were taken to test renal and liver function,and 1H NMR metabolomics test.Results1.Compared with normal group,the 24-hour urinary protein quantification was significantly increased in the model group(P<0.05),which was decreased significantly from the 19th week in Shenbingerhao prescription high-dose group(P<0.05).Compared with the normal group,the serum creatinine(Cr)and urea nitrogen(BUN)were significantly increased in the model group(P<0.05).Compared with the model group,the levels of Cr and BUN owas significantly decreaseded in Shenbingerhao prescription high-dose group(P<0.05).There were no significant difference of AST and ALT levels among all groups.2.In terms of renal pathology,the kidney structure of the normal group rats was clear,no pathological changes were observed.The model group showed mild hyperplasia in mesangial cells,increased mesangial matrix,thickened glomerular basement membrane,and swelling of some tubular epithelial cells.And the glomerular mesangial proliferation of Shenbingerhao prescription high-dose group was reduced,and the degree of mesangial matrix increase of this group was lighter than that of the model group.The structure of the tubules is basically normal.In liver pathology,except for mild fatty liver lesions in the model group,the other four groups had no obvious pathological changes.3.Metabolomics of serum showed:Compared with the normal group,the levels of 22 metabolites including 1-methylhistidine,2-hydroxybutyrate,leucine and so on increased in model group,and the levels of methionine and acetylcholine decreased.And the levels of 15 metabolites decreased after intervention of Shenbingerhao prescription.Among them,1-methylhistidine,isoleucine,lysine,vitamin D2,citric acid,alanine,creatinine,creatine,trimethylamine oxide,glycogen,histidine and glucose were recovered compared with the increase of model group,suggesting that these 12 metabolites may be the specific metabolites of Shenbingerhao prescription intervened in IgA nephropathy,which involves energy(carbohydrate,amino acids,tricarboxylic acid cycle),creatine and methylamine metabolism.ConclusionShenbingerhao prescription has the effect of preventing and treating IgA nephropathy in rats,and its mechanism is related to the regulation of metabolic disorders of IgA nephropathy,which mainly involves energy metabolism,creatine metabolism and methylamine metabolism... |
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