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The Effect Of Shen Luo Tong On Pathology And MMP-1/TIMP-1 In Tubulointerstitial Fibrosis In Rats

Posted on:2004-03-18Degree:MasterType:Thesis
Country:ChinaCandidate:Y H WangFull Text:PDF
GTID:2144360092999677Subject:Traditional Chinese Medicine
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Objective: Tubulointerstitial fibrosis (TIF) is a common pathological features of most end-stage kidney disease. The accumulation of extracellular matrix (ECM) resulting from the unbalance of synthesis and degradation is the main cause of TIF. Numbers of clinical pathology observations have shown that tubulointerstitial injury plays more important role than glomerular damage on renal failure. Because renal tubule and interstitium are intimate in structure and function, the tubular injury always accompany or follow the TIF. The reasons for TIF are as follows: Renal glomerular disease which can cause nephron ischemia ,heavy proteinuria and allergic reaction, tubulointerstitial injury resulting from various causes and interstitial nephritis, all of those can lead to TIF. Effective therapy has been looking for treatment of chronic renal failure except vicarious treatment and renal transplantation at present. And vicarious treatments such as hemodialysis and peritoneal dialysis have side effect and the pathologic lesions can not be returned. The donor for transplantation was not enough, and the patients have to suffer serious rejection with it. Only a few people can acceptthe therapy because of the expensive charge. So the mechanisms of new therapy in TIF should be studied .Angiotensin converting enzyme inhibitor (ACEI)and angiotensin Ⅱ receptor blocker(ARB) are used widely which have been proved that they can protect the renal function. The treatment of ACEI and ARB is only one way to kidney diseases which were caused by different pathogenesis. Furthermore, ACEI and ARB have renal damage on the aged. So looking for safe drugs which can inhibit the progress of TIF through different pathway and stage is of great significance. Chinese herbal compound has many therapeutical effects through different pathway, but the mechanism is still unknown.Shen Luo Tong is a basic formulla for chronic nephropathy which has the effect of alleviating the symptom and protecting the renal function. The study was to investigate the effect of Shen Luo Tong and valsartan(a drug of ARB)in rats with unilateral ureteral obstruction(UUO). The renal pathomorphism, transforming growth factorβ1(TGFβ1), collagenⅢ(ColⅢ), matrix metalloproteinases-1(MMP-1), tissue inhibitor of metalloproteinases-1(TIMP-1)were examined. Methods: Fifty female Sprague-Dawley rats were randomly divided into five groups (n=10),Sham-operation (SHAM), model(UUO), Shen Luo Tong(UUOS), Valsartan(UUOV), Shen Luo Tong plus Valsartan(UUOSV).Each animal was ligated left ureter except SHAM group. Drugs were administered from the day before operation but the saline were used in SHAM and UUO groups by oral. Animals were sacrificed after twenty-one days, the left kidneys were harvested for pathological study. Immunohistochemistry staining and in situ hybridization were used for expression of TGFβ1,ColⅢ,MMP-1 and TIMP-1.Results:(1)pathology: The renal tissue were stained with HE and Masson. There was no change in SHAM group. But in UUO group, interstitial macrophage and monocyt infiltration, renal tubular atrophy, emphraxis or expand were shown. The number of glomeruli reduced markedly, and the area of glomeruli decreased. The renal capsule adhered or expanded. Fibrous tissues proliferated around the renal capsule. While the lesions in treatment groups were slighter than that in UUO group. Pathologic image analysis shows: In UUO group, the area of fibrosis expanded significantly; the area of fibrosis in UUOS, UUOV, UUOSV groups were decreased markedly compared with the UUO group(P<0.05, P<0.01,P<0.01). It means that Shen Luo Tong and Valsartan can inhibit fibrosis in obstructive nephropathy. Among them, the inhibition of UUOS group was stronger than that of UUOV group, and the inhibition of UUOSV group was stronger than that of UUOS group, but there was no difference between them(P>0.05);While the inhibition ofUUOSV group was stronger than that of UUOV group(P<0.05).(2)The expression, distr...
Keywords/Search Tags:unilateral ureteral obstruction, tubulointerstitial fibrosis, Shen Luo Tong, extracellular matrix, matrix metalloproteinases-1, tissue inhibitor of metalloproteinases-1, transforming growth factorβ1
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