Effect Of Oxymatrine On The Renal Of Insulin Resistance Rats Induced By A High-fat Diet And The Mechanism

Objective: To investigate the effect of Oxymatrine on the renal fibrosis of insulin resistance rats induced by a high-fat diet and the mechanism.Methods: 48 male Sprapue-Dawley(SD)rats were randomly divided into normal control group(Con)(n=12)and high-fat fed group(HF)(n=36),after one-week adaptive feed,gave them standard diet and high-fat diet for 8 weeks to induce insulin resistance model.Selective 6 rats in each group and use the hyperinsulinaemic-euglycaemic clamp to judge the model were builded successfully.Then further divided the left 36 rats into six groups(n=6):normal control group(Con),high-fat fed group(HF),oxymatrine of low/middle/high dose group(OMT-L/OMT-M/OMT-H)and pioglitazone group(Pio).After given drugs ten weeks,observe body weight,food intake glucose(FBG),Cr,BUN,TC,TG,glycosylated hemoglobin(HbA1c),related protein expression,HE staining and electron micrographs.Results:1 Changes after 8 weeks high-fat feeding:(1)Body weight and average food intake: There was no significant difference between Con group and HF group in body weight at the beginning of the experiment.After 8-week of high-fat feeding,the body weight of Con group was significantly higher compared with Con group(P<0.05).But there was no statistically difference in one-day food intake between two groups(P>0.05).The results indicate that the increase of body weight as a result of high-fat feeding was independent of changes in daily food intake.(2)Blood biochemical assays: Compared with Con group,FBG,FINS,Cr,BUN,TC,TG,and TG were significantly increased in HF group.The differences were all statistically significant(P<0.05).(3)Type ? collagen:Compared with control group,type ? collagen in the rat kidney tissue of high-fat diet group significantly increased,The difference was statistically significant(P<0.05).(4)Euglycemic hyperinsulinemic clamp: The first thing was to calculate the glucose infusion rate of each group.Compared with Con group,the GIR was significantly lower in HF group(40% decreased).The difference was statistically significant(P<0.05).The results above indicate that high-fat fed rats were definitely insulin resistance.2 Changes after drug administration for 10 weeks:(1)Body weight and average food intake: At the end of 10 th week,the body weight in HF group was significantly higher than that in Con group(P<0.05).The body weight of pioglitazone and OMT groups was significantly lower compared with HF group(P<0.05),but higher than Con group(P<0.05).Compared with Con group,the average food intake per day showed a significant increase in HF group(P<0.05).However,there was no statistically difference among pioglitazone group,OMT groups,HF group and Con group(P>0.05).The results above indicate that OMT treatment could reduce body weight independent of changes in daily food intake.(2)Blood biochemical assays:Compared with Con group,the FBG,TC,TG,Cr and BUN,Hb A1 c,were significantly increased in HF group(P<0.05).After the treatment of Oxymatrine and pioglitazone,the FBG,TC,TG,Cr,BUN and HbA1 c were significantly lower than HF group(P<0.05),but still higher than Con group(P<0.05).The resuts above indicated that OMT showed more effectlly in lowering lipid than pioglitazone.(3)Type ? collagen : Compared with control group,type ? collagen in the rat kidney tissue of high-fat diet group significantly increased,the difference was statistically significant(P<0.05).After OMT and pioglitazone treatment,type ? collagen was significantly lower compared with HF group(P<0.05),but still higher than Con group(P<0.05).(4)HE staining of kidney: Six groups of rats renal tissues was observed by light microscopy at high magnification(×400).There were no obviously abnormal in the con group.In the HF group,Glomerular volume are small,the number of cells increased obviously,renal tubular epithelial cells were swelling,mesangial cells and endothelial cells were hyperplasia,mesangial area was broadening.After OMT and pioglitazone treatment,the changes above significantly reduce,but there were still differences between these two group and Con group.(5)Transmission electron microscope(TEM): There were no obviously abnormal in the renal structure of con group(×5000).In HF group,High-fat feeding group of glomerular capillary lumen atresia,podocyte foot process fusion or even disappear,uneven part of the basement membrane thickening,mesangial cell proliferation and mesangial area broadening,renal tubular microvilli,nucleus pycnosis,cytoplasm cytolysosome and cellular debris.Mitochondria swelling in the renal tubular epithelial cells,the part in vacuoles degeneration,mitochondrial cristae disorder,dissolved or even rupture,extracellular matrix.After the treatment of OMT and pioglitazone,the changes above significantly reduce,but there were still differences between these two group and Con group.(6)The related enzyme and regulating factor of renal fibrosis:Compared with control group,protein expression of TGF-?1and TIMP-2 in high-fat fed group increased significantly(P<0.05),the protein expression of MMP-2 significantly lowered(P<0.05).TGF-?1 and TIMP-2 protein expression in OMT groups and pioglitazone group was lower than HF group,while the expression of MMP-2 was higher than HF group,difference was statistically significant(P<0.05).Conclusions:1.High fat diet can lead to insulin resistance in rats,characterized by high insulin hematic disease,high cholesterol,high blood sugar and insulin resistance.2.Oxymatrine can improve glucose metabolism,lipid metabolism disorders,reduce renal fibrosis and improve kidney function.3.Oxymatrine may relieve renal fibrosis through inhibiting the protein expression of TGF-?1 and TIMP-2 in kidney,and increasing protein expression of MMP-2.