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Expression And Significance Of ILK And Correlation Factor In The Animal Model Of Renal Interstitial Fibrosis

Posted on:2009-02-15Degree:MasterType:Thesis
Country:ChinaCandidate:Z F LinFull Text:PDF
GTID:2144360245485586Subject:Internal Medicine
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Objective: Renal interstitial fibrosis(RIF) is caused and formed by many kinds of reasons that extra cellular matrix(ECM) is excessive accumulation and myofibroblast(Myof) is excessive proliferation in renal interstitium. Renal interstitial fibrosis is common pathway and major pathology foundation which is various kinds of renal diseases to evolve the end stage of renal disease. Myofibroblast that expressα- smooth muscle actin is major effective cell to compose extra cellular matrix. Emerging evidence suggests that in the process of renal interstitial fibrosis, about thirty six percentage of myofibroblast come from tubular epithelial cell to change myofibroblast. This process is named epithelial to myofibroblast transdifferentiation(EMT). Transform growth factor-β1(TGF-β1) is generally acknowledged to cause fibrosis factor. It may induce that extra cellular matrix happen and develop through many signal conduct path. Integrin -linked kinase(ILK) is major effective cell of signal conduct path of transform growth factor-β1.It participate kinds of committed step that transform growth factor-β1 induce epithelial to myofibroblast transdifferentiation.To cause renal interstitial fibrosis happening.To observe histopathology and immunohistochemistry ,to do RT-PCR method ,we can comprehend that expression of ILK and TGF-β1,α- smooth muscle actin in the animal modelof renal interstitial fibrosis,and investigate relationship between them and renal interstitial fibrosis. Methods:1. Construction of the animal modelof renal interstitial fibrosis: to select clearing SD rat seventy two,to divide randomly thrid group:control group, sham operated group, operated goup. Operated goup use unilateral ureter obstruction experiment method ,named UUO. operated goup. ligate left ureter which adjoin left renal anus perineum ;sham operated group only open abdominal cavity,and dissociation left ureter. Thrid group rat was sacrificed respectively after operatation in ond day ,thrid day, seven day , fourteen day .we take them left renal.To observe the left renal shap by our eye and renal histopathology and the degree of renal interstitial fibrosis2.Using immunohistochemistry method to detect expression of ILK and correlation factor in the animal model of renal interstitial fibrosis and to analyze relationship between ILK and TGF-β1,α- smooth muscle actin and renal interstitial fibrosis.3. Using RT-PCR method to detect expression of ILK mRNA in the animal model of renal interstitial fibrosis and to analyze relationship between ILK mRNA and renal interstitial fibrosis.Results:1.Construction of the animal model of renal interstitial fibrosis is success by ureter obstruction experiment method.2. Renal histopathology change : to compare control group , the renal of sham operated group and operated.goup is significantly intumescence and thinningz renal cortex .There are a great quantity urine to exist in the renal pelvis and to accumulate more and more with time prolong. 3.Using immunohistochemistry method to detect expression of ILK and TGF-β1,α- smooth muscle actin: ILK was rarely detected in control group, and the expression of ILK increased gradually in other groups with the degree of renal interstitial pathological injury (r=0.842,P<0.001). A significant positive correlation was found between the expression of ILK in renal tubulointerstitial tissue and the degree of renal tubulointerstitial pathological injury ( P<0.001). (2) TGF-β1 was rarely detected in control group, and the expression of TGF-β1 increased gradually in other groups with the degree of renal interstitial pathological injury (P<0.001). A significant positive correlation was found between the expression of TGF-β1 in renal tubulointerstitial tissue and the degree of renal tubulointerstitial pathological injury (r=0.892, P<0.001). (3) At normal control group, Only expressesα-SMA in the blood vessel smooth muscle has very few expression the renal interrenal .Aggravates the expression enhancement along with the renal interrenal pathological change, A significant positive correlation was found between the expression ofα- SMA in renal tubulointerstitial tissue and the degree of renal tubulointerstitial pathological injury (r=0.854,P<0.001).Conclusion:1.ILK as major effective cell of signal conduct path of transform growth factor-β1 participate kinds of committed step that transform growth factor-β1 induce epithelial to myofibroblast transdifferentiation.EMT may be a important way to lead to renal interstitial fibrosis(RIF).2.TGF-β1 appear to be important in the genesis of renal interstitial fibrosis. TGF-β1 might induces renal interstitial fibrosis by EMT.3.α-SMA as labelling proteinum of myofibroblast participate kinds of committed step that transform growth factor-β1 induce epithelial to myofibroblast transdifferentiation.α-SMA play an important role in ithe process of renal interstitial fibrosis.4.In all degrees of renal interstitial pathological injury, A significant positive correlation was found between the expression of ILK and TGF-β1α-SMA. ILK may be participate in the formation of renal interstitial fibrosis, via the induction renal tubular epithelial to myofibroblast transformation (EMT).
Keywords/Search Tags:Integrin -linked kinase (ILK), epithelial to myofibroblast transformation(EMT), renal interstitial fibrosis (RIF), transform growth factorβ1(TGF-β1), α- smooth muscle actin(α-SMA)
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