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Beneficial Effect Of Deferoxamine In The Treatment Of Ischemic Acute Renal Failure Rats

Posted on:2009-03-31Degree:MasterType:Thesis
Country:ChinaCandidate:T LiuFull Text:PDF
GTID:2144360245968948Subject:Renal disease
Abstract/Summary:PDF Full Text Request
Objective: To explore the protective effects and mechanism of deferoxamine (DFO) in ischemic acute renal failure(iARF) rats and provide experimental theory basis for the DFO's clinical application of iARF .Methods:1,Establishment of iARF rat model. Bilateral clipping of renal arteries for 45min.2,Thirty-six male Wistar rats were randomly and averagely divided into three groups : sham,surgery and DFO+ surgery groups. In surgery group,ischemic acute renal failure model was established by bilateral clipping of renal arteries for 45min and reperfusion for 24 hours.Observe the color of renal when it from dark red into bright red that means reperfusion success(the temperature of experimental animals maintained at around 37℃in this process), keeping after close abdominal cavity, and injected the rat with the same size saline throuh intraperitoneal 24 hours before the modle was established. In group sham, find renal arteries but not clip,,the other protocals were same as group model. In group DFO+ surgery,DFO was intraperitoneal injected (200mg/kg) to rats 24h before 45 min renal ischemia,the other protocals were same as group model. Activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA), blood urea nitrogen (BUN),serum creatinine (Scr) were examined.Structure of the kidney was observed under optical microscope.The expression of HIF-1α,HO-1 was detected by immunohistochemistry .Results:1,Morphological changes of renal tissue general: In Sham group renal tissue was normal; in surgery group, the appearance of kidney was saw enlargement section ,cortical swelling,pale color, medulla was dark red; the appearance of kidney was almost normal in DFO + surgery group. Histopathological changes(HE): Normal morphology was observed by optical microscopy in group sham. Red blood cells in glomerulus were seen and swelling cells of renal tubules appeared without inflammatory cell infiltrated and necrosis foci in group surgery. Only red blood cells in glomerulus were seen in group DFO + surgery group.2,Twenty- four hour after reperfusion,the levels of BUN and Scr were significantly higher in the surgery group than in the sham group(P﹤0.01),but the levels of BUN and Scr were marked downturn in the DFO + surgey group than in the surgery3,Twenty- four hour after reperfusion,the content of MDA were significantly higher in the surgery group than in the sham group,but the content of MDA were marked downturn in the DFO + surgey group than in the surgery(P﹤0.01).SOD just the opposite(P<0.01).4,Immunohistochemical study showed that the levels of HIF-1αwas positive expression in the nuclear and in the plasma ,and the levels of HO-1 was positive expression in the plasma and surface of cava of renal tubule cells. There is no positive staining in group sham.Tubule cells expressed low levels of HIF-1α,HO-1 protein in group surgery,the highest levels of HIF-1α,HO-1 were detected in group DFO+ surgery.Glomerulus and interstitial cells were not staind. Image analysis showed that difference between the two groups was significant (P<0.01).Conclusion:1,DFO pretreatment can significantly reduce the injury of renal function and the pathological extent of renal tubular injury in iARF rats.2,DFO pretreatment can protect iARF rats by clearing the free radical and inducing the over-expression of hypoxia factor-1αand hemeoxygenase-1.
Keywords/Search Tags:ischemic acute renal failure, deferoxamine, oxygen free radicals, hypoxia inducible factor-1α, hemeoxygenase-1
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