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The Effect Of Fuzhenghuayujangzhuotongluofang On The Expression Of MMP-9,TIMP-1 And COL-IV In Renal Tissue Of Rats With 5/6 Nephrectomy

Posted on:2019-10-17Degree:MasterType:Thesis
Country:ChinaCandidate:J WangFull Text:PDF
GTID:2394330566495016Subject:Integrative Medicine
Abstract/Summary:PDF Full Text Request
Research background:Chronic kidney disease?CKD?is a common and frequently occurring disease that endangers public health.The total prevalence rate of CKD in China is 10.8%,and the patients are expected to be close to 120 million,with the incidence rate being equal to that of the countries in the country and Europe,while most patients are in the1-2 period[1].Renal fibrosis is the common pathway and pathologic basis of chronic renal disease progression to end-stage renal failure.In the development of chronic kidney disease,the degradation of extracellular matrix is decreased,and the synthesis increase becomes the common pathway of renal fibrosis.Matrix metalloprotein enzyme?MMPs?is the most important enzyme system regulating ECM[2].In the process of renal fibrosis caused MMPs expression/TIMP-1 TIMPs imbalances that can lead to the ECM accumulation,excessive accumulation of extracellular matrix could result in renal fibrosis,therefore,in maintaining the balance of synthesis and degradation of extracellular matrix in MMPs/TIMPs system it is particularly important to the balance of[3].In recent years,traditional Chinese medicine has achieved good results in the prevention and treatment of renal fibrosis.On the basis of traditional Chinese medicine theory guidance,the unique role and advantages of natural medicine are given full play.This experiment is to"renal"and"rhubarbworm pill"as the foundation,composition"and complementary and used,both"centralizer blood material t2dm,for clinical trial,the antioxidant effect of renal fibrosis,delay progression of chronic kidney disease?CKD?is a plus,but the specific mechanism still needs further research,this topic proposed by righting blood material only strengthen party intervention therapy on 5/6 nephrectomy rats,study the centralizer blood material only strengthen party on 5/6 nephrectomy rat kidney tissues,MMP-9and TIMP-1 Col IV expression,the effect of further study of its delay mechanism of renal fibrosis and provide theoretical basis for clinic.Materials and methods:Male SD rats 109,weight?190±20?g,and were randomly divided into sham operation group,model group,model+fuzheng?low,medium and high dose group?.Specific methods:build 5/6 nephrectomy renal fibrosis animal model,to the centralizer blood material only strengthen party?low,middle and high dose?intervention treatment,2 weeks after lavage,respectively in gastric 4,8,12 weeks executed in rats,observe the general situation of rats,water amount,weight,diet,mental state,behavior,fully automatic biochemical analyzer,urea nitrogen,creatinine,urine routine,He,Msson,PASM staining to observe the renal pathological changes,immunohistochemical detection,MMP-9 and TIMP-1 Col-IV.Results:1.Results of Scr and BUN:comparison of Scr and BUN in the model group and sham operation group?P<0.01?showed that the model was successful;The comparison of Scr and BUN level with the model group was significant?P<0.01?.2.Results of renal pathology:the glomerular structure of the rats in the sham operation group was intact,and no obvious abnormalities were observed in the mesofilm and basement membrane.The tubular structure of the renal tubular was normal,andtherewasnoobviousinflammationandfibrosisinthe interstitium.Compared with the sham operation group,the glomerular mesangial cells proliferated in the model group,the mesangial matrix was increased,the basement membrane was obviously thickened,and the renalcapsule cavity was significantly enlarged,and the focal glomerulosclerosis was present.Part of the renal tubular epithelial cells shed,some of the renal tubules dilated,the renal tubules atrophy,and the interstitium showed inflammatory infiltration and fibrosis.There were mild hyperplasia of the glomerular mesangium in the Chinese medicine group,and the basement membrane was significantly thickened and relatively mild,and the renal tubular dilation,renal tubule atrophy,interstitial inflammatory infiltration and fibrosis were less than those of the model group.There was no significant difference between the TCM groups.3.Immunohistochemical results showed that:?1?expression of mmp-9 in the renal tissues of the rats in each group:mmp-9 was expressed in small amounts in the glomerular mesangial cells,endothelial cells and renal tubular epithelial cells and interstitial cells in the renal tissue of normal rats.Compared with the sham operation group,the expression of mmp-9 in the model group was significantly decreased,with significant difference?P<0.05?.Compared with model group,the Chinese medicine group kidney tissues increased expression of MMP-9,there were significant differences?P<0.05?,over time,4 weeks,8 weeks,12weeks of model group rats renal tissue expression of MMP-9 gradually reduce,there were significant differences?P<0.05?;There was no significant difference in mmp-9expression between Chinese traditional Chinese medicine groups?P>0.05?.?2?the expression of timp-1 in the kidney tissues of rats in each group:timp-1 was expressed in small amounts in the glomerular mesangial cells,endothelial cells and renal tubular epithelial cells and interstitial cells in normal rat kidney tissues;Compared with the sham operation group,the expression of timp-1 was significantly increased in the model group,with significant difference?P<0.05?.Compared with model group,the Chinese medicine group of renal tissue expression of TIMP-1,there were significant differences?P<0.05?,over time,4 weeks,8 weeks,12 weeks of model group rats renal tissue expression of TIMP-1,there were significant differences?P<0.05?;There was no significant difference in the expression of timp-1 in renal tissue between Chinese traditional Chinese medicine groups?P>0.05?.?3?the ratio of mmp-9/timp-1 in the kidney tissues of the rats in each group:compared with the sham group,the ratio of mmp-9/timp-1 in the model group was significantly decreased,with significant difference?P<0.05?.Compared with model group,the Chinese medicine group kidney MMP-9/TIMP-1 ratio increases,there were significant differences?P<0.05?,over time,4 weeks,8 weeks,12 weeks of model group rats kidney tissues of MMP-9/TIMP-1 ratio decreases,there were significant differences?P<0.05?;There was no significant difference in mmp-9/timp-1 ratio between Chinese traditional Chinese medicine groups,no statistical significance?P>0.05?.?4?the expression of COL-IV in the renal tissues of the rats in each group:the glomerular mesangial cells,endothelial cells and renal tubular epithelial cells and interstitial cells of the normal rat kidney were expressed in a small amount;Compared with the sham operation group,the expression of col-iv in the model group was significantly increased,with significant difference?P<0.05?.Group compared with model group,the Chinese medicine kidney COL IV expression decreased,there were significant differences?P<0.05?,over time,4 weeks,8 weeks,12 weeks of model group rats kidney COL-IV expression gradually increased,there were significant differences?P<0.05?;There was no significant difference in the expression of COL-IV in the renal tissues between the Chinese medicine groups?P>0.05?.Conclusion:1.Fuzhenghuayujangzhuotongluofang can improve the survival status of renal fibrosis rats and to delay the progress of the disease.2.Fuzhenghuayujangzhuotongluofang can significantly reduce the blood creatinine,urea nitrogen and urine protein,improve renal function and reduce the degree of fibrosis of the kidney.3.The centralizer blood material t2dm may through the 5/6 nephrectomy rats the expression of MMP-9 kidneys,inhibit the expression of TIMP-1,thus promote the degradation of COL-IV,reduces the accumulation of ECM,and delay the progress of renal fibrosis.
Keywords/Search Tags:renal fibrosis, 5/6 nephrectomy rats, MMP-9, TIMP-1, Col-IV
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