| Objective: Through clinical case collection,observing the efficacy and safety evaluation of Jianzhong Bushen Xiaozheng decoction on chronic renal failure patients with spleen and kidney deficiency and blood stasis turbidity syndrome.And through experimental research,exploring Jianzhong Bushen Xiaozheng decoction regulate WNT/β-catenin pathway based on mi RNA139 of UUO model of renal interstitial fibrosis in mice intervention effect and its mechanism of action,for the clinical application of Chinese medicine delay the diagnosis and treatment of chronic renal failure process for further thinking.Methods:(1)Clinical study: 60 clinical cases meeting the inclusion criteria and exclusion criteria were randomly divided into control group and experimental group,30 cases in each group.The control group was given symptomatic treatment of Western medicine,and the experimental group was given Jianzhong Bushen Xiaozheng Decoction on the basis of Western medicine treatment.The observation course of both groups was 8 weeks.The changes of serum creatinine(Scr),urea nitrogen(BUN),uric acid(UA),glomerular filtration rate(e GFR),hemoglobin(Hb),serum albumin(ALB),urinary protein/creatinine ratio,TCM syndrome score and total therapeutic effect were observed before,4 weeks after and 8 weeks after treatment in 2 groups.(2)Experimental study: 120 mice were randomly divided into sham operation group,UUO group,Jianzhong Bushenxiaozheng Decoction low-dose group,medium-dose group,high-dose group and Niaoduqing group,and unilateral ureteral obstruction(UUO)animal model was used.Postoperative 3 d building began to fill the stomach,the control group,UUO group every day be amount of distilled water to fill the stomach,low dose group,middle dose and high dose respectively according to 6 g/kg/d,12 g/kg/d,24 g/kg/d give Jianzhong Bushenxiaozheng Decoction lavage liquid solution,6.2 g/kg/d Niaoduqing particles liquid was gave to Niaoduqing group,observe 14 d and 21 d and 28 d after morphological changes in mice,observing the general signs and obstruction of bilateral renal interstitial fibrosis index,using HE and Masson staining to observe the pathological morphological changes of renal tissue,RT-PCR to detect the mi RNA-139 expression in the obstruction siderenal tissue,protein western blot to detect β-catenin,PAI-1 expression in the obstruction side kidney tissues,immunohistochemical detection of MMP7 protein expression.Results:(1)Clinical study: Compared with the control group,the experimental group had significant efficacy in reducing Scr,BUN,increasing e GFR,decreasing urinary protein/creatinine ratio,and improving TCM syndrome score(P<0.05),but there was no significant difference between the two groups in increasing Hb,ALB and decreasing UA levels(P>0.05).Both the experimental group and the control group could improve the overall efficacy of patients with CKD,but the experimental group was more significant in improving the efficacy of CKD efficacy than the control group(P<0.05).The results indicated that Jianzhong Bushenxiaozheng Decoction had better efficacy in improving renal function and alleviating clinical symptoms than the control group,but had similar efficacy in improving Hb,ALB and UA as the control group.(2)Experimental study:(1)Compared with the UUO group,Jianzhong Bushenxiaozheng Decoction can improve the diet,weight and other general conditions of mice,and enhance the function of spleen and stomach.(2)The levels of Scr and BUN in UUO group were significantly higher than those in sham group(P<0.05),indicating the success of modeling.Jianzhong Bushenxiaozhneg Decoction high-dose group was better than other groups in improving the levels of Scr and BUN in mice during each modeling period,and the difference was statistically significant(P<0.05).(3)The results of HE staining showed that the boundary between the skin and medulla of the kidney tissue in the sham operation group was clear,the number of renal tubules was abundant and tightly arranged,the morphology of epithelial cells was normal,the glomerular capillaries were clear,and no obvious abnormality was observed.But with the increase of time after building,UUO group was gradually expand the renal pelvis,narrow renal parenchyma,the decrease in the number of renal tubules,the dividing line is not clear,interstitial connective tissue hyperplasia in great quantities,renal tubular expansion,more narrow epithelium,a large number of renal tubule shrinkage,luminal stenosis,edema,epithelial cells of renal tubule interstitial and perivascular inflammatory cells infiltration.The Niaoduqing group and TCM groups poisonous can reduce the injury of renal tissues.(4)Masson staining showed that the structure and morphology of renal tissue in the sham operation group were normal,with a small amount of collagen deposition in the renal tubule interstitium,and no significant change in each time period.In the UUO group,a large amount of blue-purple collagen fiber deposition was observed in the kidney tissue,and the collagen deposition became more obvious with the protraction of the obstruction time,and the degree of renal fibrosis index increased(P<0.05).At the 14 th week of treatment,the renal fibrosis index of each treatment group was less than that of the UUO group(P<0.05),Chinese medicine has a certain effect on delaying renal interstitial fibrosis.(5)The results of RT-PCR showed that the expression of mi RNA139 in the UUO group was lower than that in the model group(P<0.05),mi RNA139 increased different degrees in each administration group at each stage after modeling(P<0.05),and the effect of high dose group was the best.(6)Western blot results showed that β-catenin and PAI-1 were only slightly expressed in the kidney tissues of mice in the sham operation group,but the expression of β-catenin and PAI-1 in the kidney tissues of mice in the UUO group was increased.With the prolonging of modeling time,the expression levels of β-catenin and PAI-1 in renal tissues of mice in each administration group decreased to varying degrees(P<0.05),and the effect of the high-dose group was more significant than that of the Nuduqing group(P<0.05).(7)Immunohistochemical analysis of MMP7 showed that the expression of MMP7 in the UUO group was significantly lower than that in the sham group(P<0.05),with the prolongation of modeling time,the expression of MMP7 in each administration group was increased(P<0.05),and the expression of MMP7 in high-dose group was significantly higher than that in other treatment groups.Conclusion:(1)For patients with chronic renal failure,the application of Jianzhong Bushenxiaozheng therapy has obvious effects in improving patients’ clinical symptoms,improving the efficacy of traditional Chinese medicine,improving patients’ laboratory indicators,protecting renal function and improving the quality of life of patients,and it is safe and reliable.(2)Jianzhong Bushenxiaozheng Decoction can increase the expression of mi RNA139 and MMP7,inhibit the expression of β-catenin and PAI-1,regulate the Wnt/β-catenin signaling pathway,and delay the progression of renal interstitial fibrosis. |
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