Effects Of Yishentongluo Decotion On The Expression Of Nf-κb And Mmp-2 On Experimental Membranous Nephropathy

Objective: Idiopathic Membranous Nephropathy is one of pathology types about adult nephritic syndrome, and the general age of Idiopathic Membranous Nephropathy is 40～50 years old.The pathology characteristic includes:immune complex deposit in the endepidermis of the glomerular basement membrane,and capillary basement membrane diffusely thicken; the clinical manifestation is albuminuria without complaint and nephrotic syndrome and end-stage renal disease.Excitatory autacoid and cytotoxic drug have bad curative effect and major adverse reaction.For the recent years, combined treatment of traditional Chinese medicine and western medicine is better,and can decrease effectually adverse reaction of excitatory autacoid and immunodepressant.Professor Tanjinchuan by clinical observation for many years regarded that the etiopathogenesis of Idiopathic Membranous Nephropathy was kidney psyche weakness and stagnant blood blockage. In the foundation of determine the treatment based on differentiation of symptoms and signs, he created Yishentongluo Decotion including:huangqi,dangshen,chaobaizhu,xianlingpi,dilong,shuizhi,ezhu,dang-gui,jiaogulan and so on which is predominant on clinic therapeutic effect.We induced Idiopathic Membranous Nephropathy rat animal model by C-BSA.Proteinuria plasma protein,blood-fat,renalfunction,renal pathomorphology,the expression of renal NF-ΚB and MMP-2 were observed.The effect and mechanism of Yishentongluo Decotion on Idiopathic Membranous Nephropathy were investigated so as to provide experimental data.Method:SD male mice with body weights at 160±20g were obtained from the Experimental Animal Center of the Hebei Medical Univerisity.They had free access to water and were allowed to adapt to their food and environment for 1 week before the start of the experiment,and urine protein and red blood cells were detected.The results was negative.Then they were randomly divided into four groups:Normal,Model, Benazepril and traditional Chinese medicine(TCM) group (n=10,in each group).The group of Model and Benazepril and TCM were immunized with C-BSA(three times a week,three weeks) from the third week to make Idiopathic Membranous Nephropathy rat animal model after force-immunity for one week,while the normal group intraperitoneally injected with the same volume of saline only.24h urine protein was determined. Benazepril group:Benazepril via oral administration at a dosage of 10mg/kg/d for 4 weeks. TCM group:Yishentongluo Decotion via oral administration at a dosage of 5ml/kg/d for 4 weeks.After 4 weeks, all of the animals were killed and blood collected from the femoral artery.24h urine protein was determined with the trichloroacetic acid tubidimetry.Serum TP, Alb, TC, TG, BUN, and Scr were assayed with the automaticbio chemistry analyzer.Blood viscosity, hematoplasma viscosity and volume packed cells were detected by blood viscosity instrument.Each group of glomerular basement membrane and foot process were observed with light microscope and electron microscope.The expression of NF-κB and MMP-2 were observed with the immunohistochemical staining.The section of HE,Masson,PAS staining and immunohisto-chemistry staining was analyzed with the pathology image analysis system.Result:(1) 24h urinary protein quantitative analysis showed that:After injected with C-BSA(three times a week,three weeks), Model, Benazepril and TCM group were significantly higher than Normal group (P<0.05).After intragastric administration for four weeks, the 24h urinary protein quantitative analysis of Benazepril and TCM group was sharply decreased with the Model group(P<0.05) and the TCM group was better than the Benazepril group(P<0.05).(2)Biochemistry analysis after intragastric administration for four weeks:TP and Alb of the blood serm in Model,Benazepril and TCM group were descent significantly than Normal group(P<0.05).The Benazepril and TCM group were significantly higher than Model group(P<0.05).There was significant difference between Benazepril and TCM group(P<0.05) and TCM group was higher than Benazepril group in the level of TP and Alb.The level of TC and TG was markly increased in Model, Benazepril and TCM group compared with Normal group(P<0.05).The level of TC and TG of Benazepril and TCM group were lower than Model group(P<0.05).The TCM group was the lowest group in the level of TC and TG (P<0.05). There was no significant difference in Model,Benazepril,TCM and Normal group before and after the treatment in the level of BUN and Scr(P>0.05).(3)Nephridial tissue pathomorphology showed that: The light microscope observation result showed that : The structure of renal glomerulus in the Normal group was normal. In the Model group, the glomerular capillary walls and glomerular basement membrane thickened, and a little of lymphocyte and monocyte was infiltrated in renal interstitium. The electron microscope observation result showed that: much electron point deposited in the glomerular basement membrane, and foot processes fused. Immunofluorescence observation result showed that: IgG and C3 granulo-deposited in glomerular capillary wall and mesenterium. Benazepril and TCM group were lessener the changes of renal pathology compared to the Model group.(4) Immunohistochemical findings of NF-κB and MMP-2: NF-κB was expressed ,at a low level, in tubular epithelial cells and podocytes of Normal group,while at a high level in Model, Benazepril and TCM group.The expression of NF-κB in Model group increased as compared to the Benazepril and TCM group(P<0.05).MMP-2 was expressed as buffy particle in the nephric tubule epithelial cell endochylema in four groups. But MMP-2 in the Model group increased as compared to other groups.There was no markly difference of MMP-2 expression between the Benazepril and TCM group.The Normal group expressed MMP-2 the least in the renal glomerulus.Conclusion:1 Yishentongluo Decotion can reduce rat's proteinuria, increase plasma protein, improve blood rheology.2 Yishentongluo Decotion can depress NF-κB and MMP-2 expression in nephridial tissue, lighten podocytes fusion, and enhance recovery of glomcrulus basal membrane. So Yishentongluo Decotion can lighten nephritic injury and delay the progression of disease.3 Yishentongluo Decotion is better than Benazepril in the effect of treating Idiopathic Membranous Nephropathy.