| Objective:1.To review the research advancement on the chronic renal failure(CRF) treat with traditional Chinese medicine(TCM).2.To explore the mechanism of action of Jianpiyishen Decotion on renal fibrosis and provide experimental evidence for clinical application.3.To observe the clinical efficacy on CRF and anti-renal fibrosis of Jianpiyishen Decotion.Methods:1.Literature study:To look up a great deal of ancient and modern time literature and summarize the research status of pathogenesis of TCM and determination of treatment based in pathogenesis obtained through differentiation of symptoms and signs on CRF.2.Experimental study:The Wistar male rats were divided into four groups randomly.They were normal control group(N group),model group(M group), low dose treatment group(L group)and high dose treatment group(H group). All the rats were made animal model of CRF with subtotal renal ablation except the N group.Interfere the rats one week after the operation.The N group and M group were given 1ml normal saline by intragastric administration.The L group was given 1ml Jianpiyishen Decotion concentrated solution and the H group was given 4ml by intragastric administration.After being interfered for 8 weeks,take the 24h urine,blood serum and nephridial tissue.Detect serum urea nitrogen(BUN)and creatinine(Scr)with automatic biochemistry analyzer.Detect the expression of Lectin-like Oxidized Low Density Lipoprotein(Lox-1)mRNA and the transforming growth factor-β1(TGF-β1) mRNA with RT-PCR and detect the expression of TGF-β1,α- smooth muscle actin (α-SMA)and fibronectin(FN)with immunohistochemistry.Detect the urea TGF-β1 with the enzyme-linked immunosorbent assay(ELISA)。3.Clinical research:Select 80 patients of CRF in compensation and decompensation stage.Divide them into treatment group(42 persons)and control group(38 persons)randomly.Both groups were given the same therapy such as anti-infection,retrieve the imbalance of water,electrolytes and acid base,control the blood pressure,high-quality low protein and low phosphonium food and drink,keep enough energy supply,etc.Give one dose Jianpiyishen decotion to the treatment group everyday and take it twice orally.While give 10mg benazepril to the control group everyday.Observe the change of cardinal symptom integral,renal function and urea TGF-β1.Results:1.Literature study:The cause of CRF is complicated.Mainly belong to asthenia in origin and asthenia.in superficiality.Asthenia of healthy energy include the deficiency or damage of Qi,blood,Yin,Yang,Zang and Fu organs, especially because the deficiency of the spleen and kidney.State of evil domination include pathogenic damp,stagnanted blood and ulcerated edema.The earlier period appearance is asdthenic splenonephro-Yang and mainly because the asthenia of healthy energy.And the later period appearance is deficiency syndrome mingling with excess syndrome,decline of kidney-Yang and turbid pathogenic factor congestion,and the state of evil domination is outstanding. The substance is asthenia of healthy energy and the appearance is state of evil domination.The asthenia and sthenia,cold and heat are dynamic changing. The illness position of CRF is spleen and kidney.2.Experimental study:(1)Renal function detection:After 8 weeks,the rat serum BUN and Cr of M,L and H group increased significantly compared with N group(P＜0.01).The BUN and Scr of M group increased more than L and H group,the difference were significant(BUN:M VS L group and M VS H group,P＜0.01;Scr:M VS L group,P＜0.05,M VS H group P＜0.01).There was no significant difference between L group and H group (P＞0.05).(2)RT-PCR detection: There was expression of Lox-1 mRNA in rats' kidney in each group.The expression in N group was.weaker,while there were significant increase in M,L and H group than N group(M,L VS N group:P＜0.01,H VS N group:P＜0.05).The expression in L and H group decreased significantly than M group (P＜0.01).The expression in H group was,less than L group(P＜0.05).There was expression of TGF-β1 mRNA in rats' kidney in each group.The expression in N group was weaker,while there were significant increase in M and L group than in N group(P＜0.01).There were no significant difference between H and N group(P＞0.05).The expression in L and H group decreased more than in M group obviously(P＜0.01),and in H group it decreased more than in L group obviously(P＜0.01).(3)Immunohistochemistry detection:①the expression of TGF-β1:There was weak expression in glomerular endothelial cell,capillary endothelium cell and renal tubular epithelial cell in N group.There was high expression in the above-mentioned positions in M group,and there was significant difference in M group compare with N group (P＜0.01).There was medium intensity expression in these sites in L and H group,and the expression' s increase had statistical significance compare with N group(P＜0.01),while the decrease of expression had statistical significance compared with M group(P＜0.01).The expression in H group was lower than L group(P＜0.05).②the expression ofα-SMA:In N group,there was no expression in renal interstitium,nephric tubule and surroundings,glomcrulus,but in renal interstitium blood vessel and afferent arteriole of glomerulus vessel wall the expression was positive.In M group,the expressions in renal interstitium and renal tubular epithelial cell were strong positive,and there was expression in glomcrulus too.The expression increased more than N group(P＜0.01).There were medium intensity expression in renal interstitium and renal tubular epithelial cell in L and H group.The expression increased more than N group(P＜0.01),and it decreased more than M group(P＜0.01).The expression in H group was lower than L group(P＜0.05).③the expression of FN:In N group,there were light expression in renal tubulointerstitial substance,cellula epithelialis basal membrane and vascular smooth muscle.In M group,there were strong expression in renal tubulointerstitial substance and renal tubule,and there was expression in glomerular mesangium.There was significant difference between N and M group (P＜0.01)There were medium intensity expression in renal tubulointerstitial substance and renal tubule in L and H group.The expression was higher than that of N group(P＜0.01)and lower than that of M group (P＜0.01).The expression in H group was lower than in L group(P＜0.05).(4)Urea TGF-β1 ELISA detection:The concentration of urea TGF-β1 in M,L and H group increased obviously than that of N group(P＜0.01).In L and H group the concentration of urea TGF-β1 were lower than M group(P＜0.01)There was no statistically significant between H and L group.3.Clinical research:Before the treatment,there was no statistically significant between the two groups.After the treatment,the symptom of treatment group lessened obviously much more than pretherapy(P＜0.01),and the symptom of normal control lessened more than pretherapy(P＜0.05).There were significant difference between the two groups after the treatment(P＜0.01).The serum BUN and Cr levels of the two group had no difference before the treatment.After the treatment,the serum BUN and Cr levels of the treatment group decreased obviously(P＜0.01),and that of the normal control decreased (P＜0.05).The urea TGF-β1 concentration of treatment group decreased lower than normal control(P＜0.01).Conclusion:1.Literature study shows that the traditional Chinese medicine have distinct effect to CRF especially to early metaphase renal inadequacy patients. Natural plants are mainly in the traditional Chinese medicine,and they have less harm and side effect to human body.Furthermore,the strong point of TCM treatment is regulate the whole body,enhance the quality of life,postpone the advancement of the illness and increase in life span.2.The animal experiment shows that Jianpiyishen Decotion can decrease the CRF rats' serum BUN and Cr,restrain the expression of Lox-1,TGF-β1,α-SMA and FN in kidney tissue.And it indicates that Jianpiyishen Decotion is a effective herbal prescription for the treatment of CRF.The mechanism maybe because it can restrain the expression of the cell factor such as TGF-β1 in rats' kidney,decrease the generation ofα-SMA and FN.Then,it can restrain the cell multiplication and transdifferentiation which participate renal fibrosis,delay the progress of renal fibrosis and CRF.3.Clinical research shows that Jianpiyishen Decotion can improve the CRF patients' clinical symptom,decrease the serum BUN and Cr levels,and it can improve the patients' renal function.It can decrease the excrection of urea TGF-β1,and delay the renal fibrosis,thus delay the progress of CRF.All these results show that Jianpiyishen Decotion is a effective traditional Chinese medicine for preventing and curing CRF,and it is worth to be researched and developed and spread in clinic.
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