| Chronic glomerulonephritis(CGN) is a common autoimmune inflammatory disease in clinical,the pathological mechanisms and treatment of it has been the research hotspots. Ubiquitin-proteasome pathway(UPP)is a efficient,specific and energy-dependent Proteolytic pathway. Nuclear Factor-kappa B(NF-κB)is the center of the inflammatory response network,and its activation is strongly depend on UPP.Therefore,there is a surmise that UPP and NF-Kb are related to CGN.Zhenwu decoction is a representative Formula of Warming Yang to Promote Diuresis from Shang Han Lun. Although there is a large number of experimental and clinical data to demonstrate the therapeutic effect on CGN,pharmacological mechanism should be further clarify for clinical application. CGN model are induced by repeated doses of cationic bovine serum albumin(C-BSA),which has a similar clinical course and histopathology to human CGN.However,there are many limitations in the preparation process of the model,such as repeated injection, time-consuming, difficult to operate, and low possibility of success.Osmotic pumps are miniature,implantable pumps and can deliver reagent at continuous and controlled rates, and the application of C-BSA osmotic pump in the reproduction of CGN model can overcome those difficulties.Objective1 To further improve application of the osmotic pump in CGN models,make CGN model by using C-BSA osmotic pump.2 On the basis of CGN model induced by C-BSA osmotic pump, observe the protective effect of Zhenwu Decoction on the kidneys of CGN model rats.3 To investigate the pathogenesis of CGN at the gene level,and expound the treatment mechanism of Zhenwu decoction on CGN,detect related molecules of UPP and NF-κB,and inspect the intervention of Zhenwu decoction on it.MethodsPrepare C-BSA according to Border and CGN model induced by C-BSA osmotic pump, and the CGN model rats were be treated with Zhenwu decoction.1 Study the therapeutic effect of Zhenwu decoction on CGN ratsObserve the general condition,detecte some related indicators and observe the kidney pathological features and the ImmunoglobulinG(IgG) level.The related indicators including urine protein,urine creatinine(SCr),total serum protein(TP),serum albumin(ALB), serum SCr,blood urea nitrogen(BUN),total serum cholesterol(TC), serum triglyceride(TG), serum nitric oxide(NO), serum superoxide dismutase(SOD),and serum maleic dialdehyde(MDA).2 the condition of NF-κB activation in rats kidneyInspect the content of Tumor Necrosis Factor-alpha(TNF-α) and Interleukin-1 beta(IL-1β) in serum and kidney,the expression and distribution of TNF-α,NF-κB in kidney,the mRNA expression of NF-κB p65,IκB in kidney, and the DNA binding activity of NF-κB.3 Exam the UPP pathway in rats kidneyInspect he expression and distribution of Ubiquitin in kidney,the mRNA expression of Ubquitin and Ubiquitin Conjugating Enzyme(E2) in kidney.Results1 The treatment of Warming Yang to Promote Diuresis on glomerulonephritis model rats induced by C-BSA osmotic pumpCompared to CGN model group,rats in possessed a better mental condition,a better diet,a better hair sheen and better active state;the 24h urine protein of Zhenwu decoction treated rats was obviously induced(P<0.01);the 24h urine creatinine of rats treated by Zhenwu decoction of high dose and middle dose was obviously improved (P<0.01 or P<0.05);the TP of Zhenwu decoction treated rats was obviously improved (P<0.01 or P<0.05); the serum ALB of Zhenwu decoction high dosage group increased(P<0.05);the serum creatinine of high and middle dose group rats obviously induced (P<0.01 or P<0.05);the BUN of high dosage group rats obviously improved(P<0.01);the serum TC of high dosage group rats induced (P<0.05);the serum TG of high and middle dosage groups remarkably induced(P<0.01 or P<0.05);the level of serum NO of Zhenwu decoction treated rats markedly increased(P<0.01);the level of serum SOD and MDA of Zhenwu decoction treated rats obviously improved;Zhenwu decoction,especially high dosage group, could restore glomerular structure inordinately;the status improved by Zhenwu decoction,such as the diffuse irregular thickening of glomerular basement membrane, a lot of electronic sediments,swelling of the epithelial cells;Zhenwu decoction reduced the expression of glomerular IgG.2 The intervention of Warming Yang to Promote Diuresis on NF-Kb of CGN rats induced by C-BSA osmotic pump.Zhenwu decoction significantly reduced the content of TNF-a and IL-1βin serum and kidney of CGN rats(P<0.01);obviously reduced the expression of TNF-α、NF-κB in kidney;Zhenwu decoction high and middle dosage groups reduced the expression of NF-κB p65 mRNA,improved the expression of 1-Kb mRNA (P<0.01 or P<0.05); Zhenwu decoction significantly reduced the DNA binding activity of NF-κB.3 The intervention of Warming Yang to Promote Diuresis on UPP pathway of CGN rats induced by C-BSA osmotic pump.Zhenwu decoction obviously reduced the expression of Ubiquitin in kidney; Zhenwu decoction high and middle dosage groups reduced the expression of Ubiquitin mRNA ((P<0.01 or P<0.05); Zhenwu decoction significantly reduced the expression of E2 mRNA (P<0.01 or P<0.05)Conclusions1 There ia a significant protective effect of Zhenwu decoction,representing the method of Warming yang to promte diuresis on glomerulonephritis model rats induced by C-BSA osmotic pump.2 Zhenwu decoction,representing the method of Warming Yang to Promte Dieresis can block UPP pathway,and inhibit the activation of NF-κB,which is associated with the treatment of Zhenwu Decoction on glomerulonephritis model rats... |
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