Experimental Study Of The Kidney And Slow Decline Of The Tubulointerstitial Fibrosis

Background:renal tubulointerstitial fibrosis TIF is various kidney trouble that develops to latter stage of end common behavior and main pathologic foundation of nephropathy,it is a depleted common route of the renal function.It is tubular epithelial cell degeneration,atrophy,disappeared in the interstitial lymphocytes and monocyte infiltration,gathered at the same time a large number of myofibroblasts and extracellular matrix as the main feature.In the 20th century people of the long years of research on kidney disease,glomerular diseases understanding of the relative depth, and on tubulointerstitial pathological changes of a relatively small,and even ignored. In the 20th century,after 1990s,the first such discovery since the Risdon GFR decline and tubular atrophy was positively correlated with the glomerular damage has been no obvious correlation,more and more studies have shown that renal tubular damage and Mesenchymal pathological changes is closely related to the extent.In end-stage renal disease(ESRD) patients in the renal tubulointerstitial incidence of the disease accounting for 20%to 30%,and in a variety of common development of the glomerular diseases are associated with different stages of varying degrees of renal tubular Mesenchymal damage.A large number of clinical and experimental studies demonstrating the tubulointerstitial damage and the relevance of renal glomerular lesions than more closely reflect the severity of the decline in renal function and determine the most important prognostic indicators.Therefore,we can consider that progress in the course of CKD,tubulointerstitial damage than glomerular lesions plays a more important role,and determine the prognosis of CKD.Accordingly,renal interstitial fibrosis formation mechanism and prevention measures,the clinical finding can prevent or slow renal interstitial fibrosis drug is of great significance.Kidney failure to alleviate the hospital compound as agents for the treatment of chronic renal failure nearly 20 years,and have achieved good clinical efficacy.Astragalus major drug component Yousheng,ginseng,angelica,Chuanxiong,TPG,Poria Spatholobus suberectus,cooked rhubarb,and so on,is a nourishing and promoting blood circulation Yiqi,Lishi diarrhoea muddy compound of the power of Chinese medicine. Section I of the study confirmed previous drug can reduce the 5 / 6 nephrectomized rats modeling residual renal ECM accumulation,inhibition factor promoting fibrosis TGF-βin the residual renal expression of glomerular sclerosis and curb improvements small tube - Mesenchymal fibrosis.Ease the decline in the 5 / 6 nephrectomized rats renal microvascular remodeling and vascular endothelial growth factor(VEGF) expression of the study confirmed that ease the bad side and angiotensin-converting enzyme receptor antagonist(Cozaar) have the duty to promote residual renal expression of VEGF and reduce loss of renal microvessels and reduce the rote of renal fibrosis,through Kidney failure to alleviate the chronic treatment of 46 cases of aristolochic acid nephropathy study we found that this may significantly delay the aristolochic acid nephropathy in patients with chronic renal function of the speed of decline.By renal biopsy in the 78 patients with CKD observation,collect relevant laboratory indicators,renal pathology data and TCM clinical data analysis,we reached the following conclusions:(1) in patients with CKD Hygrothermal card, blood stasis CKD is affecting the progress of the important factors.(2) hot and humid with blood stasis permits the link between "hot and humid folder stasis" CKD patients with Chinese medicine is an important part of syndromes.(3) CKD patients with blood stasis and tubulointerstitial injury significantly related to the existence of blood stasis is CKD patients Syndrome CKD factors affecting the progress of the most critical factors.This tubular interstitial fibrosis related to the evidence-based research, based on experimental use Yiqi Yangxue Huoxue,Lishi diarrhoea cloud of the power failure,Yishen ease,providing a solid basis for the further elaboration of Chinese medicine in renal tubular interstitial injury in the role of an important theoretical basis.Objective;This study was taken to hospital preparations Kidney failure to alleviate,irbesartan and animals sterile water unilateral ureteral ligation(UUO) of the rat model of renal fibrosis group to clear hospital preparation Yishen failure to alleviate delay in the renal interstitial fibrosis and renal function in the role.UUO rats through the use of small interstitial injury model of drugs on biochemical indicators of the impact of the extent of the damage histopathology,immunohistochemistry was detected in rat kidneyα-smooth muscle actin(α-SMA),bone morphogenetic protein-7(BMP-7),the expression of both the exploration and the associated mechanisms,ease of Kidney failure,whether through regulation andα-SMA expression of BMP-7,so as to achieve ease Pathological changes in the kidney and improve renal function.Wet Yiqihuoxue benefit of the tubular interstitial fibrosis and the role of Chinese medicine in the renal interstitial fibrosis in the positive role of the CKD patients for the clinical treatment can be extended to provide an effective drug with the corresponding clinics thinking.Methods;In this experiment,180-200 g healthy male subjects Wister rats,a week after keeping animals adaptability,36 rats were randomly divided into four groups,each with 8:sham-operated group,model group,the Chinese Medicines Board,irbesartan losartan group.One model group,the Chinese Medicines and irbesartan group made UUO rat model:10%were used Chloral Hydrate(2.0 to 3.0 ml / kg) intraperitoneal injection of anesthesia,surgical field to Mao,75%ethanol disinfection,abdominal choice midline incision slightly left,followed by abdominal incision to the skin,kidney and ureter free,will be left ureter tissue forceps hold up the middle position,bleeding clamp living in the thread ends with 4-0 ureteral ligation of the left renal pelvis near paragraph and remote.Then continuous suture skin.Sham surgery group approach the same way as the model group,but after open abdominal not free ureteral ligation,or suturing the skin.Animal model group sterile drinking water to 12 ml / kg.d,sham-operated group sterile drinking water to the animals 12 ml / kg.d,Chinese medicine group:Chinese medicine to 12 ml / kg.d(equivalent to adult daily dosage per kg body weight 15 times) irbesartan group to 1 mg / ml concentration Ebeishatan solution(now with sterile water daily),12ml/kg.d,above all gavage for 10 days,one day.Section 10 d after the rats were sacrificed and blood from the femoral artery,separation of serum measured serum creatinine(Scr),blood urea nitrogen (BUN).A post-mortem in situ lavage from the left kidney,with 10%formalin-fixed, paraffin-embedded,2 um thick slices,conventional HE staining,to understand each group pathological changes,visit Masson staining,with a microscope image analysis system(Olympus ix70 inverted fluorescence microscope) and Imagepruplus image analysis system for analysis,the positive area(μm2),as statistical data,the evaluation group tubulointerstitial damage.Final results by using SPSS statistical software analyzed.Results:(1) Determination of renal function:the sham group,compared to the other three groups Scr were significantly increased(P＜0.05),the Chinese medicine and irbesartan treatment,the drop was not significant(P＞0.05).Detection and BUN, compared with the sham-operated group and the remaining three groups BUN were significantly increased(P＜0.05),but compared with the model group,the Chinese group and irbesartan group were significantly decreased(P＜0.05),the two treatment Comparison between groups,there was no significant difference.(P＞0.05).After that after treatment,Scr not obvious decline,BUN has been significantly decreased,but not to normal levels.(2) Renal pathology:the naked eye observation that:sham-operated rats kidney Anjiang color,size,shape normal.Model group,the Chinese Medicines and irbesartan ligation kidneys of rats color desalination,obviously enlarged,cystic sexy,memory tawny turbid liquid,pelvis obvious expansion,the real thinning.Optical microscopy:①HE staining,sham-operated group occasionally tubular epithelial cells degeneration,kitchen-infiltrating mononuclear cells;model group that diffuse tubular epithelial cells degeneration,some of the lumen with protein or cell type,with small foci of the expansion,contraction,occasionally necrosis,renal interstitial how stove-monocyte infiltration and fibrosis,glomerular no significant pathological changes.Chinese group and irbesartan group these changes reduce both.②Masson staining,model group that interstitial collagen fibers with large blue proliferation, glomerular lesions not obvious.Chinese group,irbesartan group renal interstitial collagen fibers positive staining area compared to the model group were significantly decreased(P＜0.01) between the two treatment groups,the difference was not statistically significant(P＞0.05). (3) Kidney ofα-SMA,the expression of BMP-7 and Change:α-SMA to leave, die,Dayang,in the expression of all groups:sham-operated group of vascular smooth muscle cell wall was strong expression,and glomerular no significant renal tubular epithelial cells coloring,renal medulla were scattered in the sparse weak positive. Model Section of the site to renal interstitial was mainly on the expansion or contraction of the tubular around,or renal interstitial fibrosis in.Chinese group and irbesartan group that is scattered renal interstitial fibrosis,a small expression of BMP-7 in the false,mould,Dayang,in the expression of all groups:sham-operated rats renal distal convoluted tubules in the pool The expression of,and strong expression in proximal tubular epithelial cells in a small amount of expression in the glomeruli basically no expression.Expression in the medulla in the cortex was significantly higher than that of expression.Rat model of renal interstitial fibrosis increasing extent,BMP-7 expression was significantly reduced;medicine group and irbesartan group rat kidney BMP - 7 expression was significantly increased compared with model than sham-operated group reduced.Conclusion:1.Kidney failure may ease significantly decreased serum urea nitrogen content, and the effect of irbesartan no significant difference.Without significantly decreased creatinine,Irbesartan is the same.2.Kidney failure,and ease irbesartan can inhibitα-smooth muscle actin(α-SMA) expression,increase bone morphogenetic protein-7(BMP-7) in UUO rat kidney tissue, inhibiting the tubular epithelial cells to divide,an increase of ECM degradation,and the difference between the two treatment groups with no statistical significance,the Kidney failure to alleviate the effects of treatment with irbesartan similar to both reduce the role of renal fibrosis.3.Kidney failure to alleviate group compared with the model group,α-SMA expression area,Masson staining of collagen fiber size were reduced,confirmed Kidney failure to reduce the ease of ECM components hyperplasia,reducing renal fibrosis disease. 4.Tubulointerstitial fibrosis in the process of renal interstitial fibrosis area and BUN,Scr were positively correlated(r=0.637,P＜0.001),suggesting that the damage and renal interstitial fibrosis associated with theα-SMA expression was positively correlated(r=0.845,P＜0.001),and the expression of BMP-7 was negatively correlated(r=-0.865,P＜0.001),andα-SMA expression of BMP-7 was negatively correlated(r=-0.983,P＜0.001).Tip Kidney failure to alleviate possible by inhibiting the expression ofα-SMA,and to increase the expression of BMP-7 to turn inhibit renal tubular epithelial differentiation,so as to reduce the degree of renal fibrosis.