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Experimental Study On Antioxidant's Protective Effect On The Kidney Of Rats With Sepsis

Posted on:2012-03-07Degree:MasterType:Thesis
Country:ChinaCandidate:D W ZhangFull Text:PDF
GTID:2154330335980991Subject:Emergency Medicine
Abstract/Summary:PDF Full Text Request
Sepsis , a phase of a disease caused by severe infection, is one of the main reasons leading to the death of people with serious disease.With the activation of neutrophile granulocyte, macrophage , the chrotoplast in the vessel, the formation of inflammatory factors in large number as well as the startover of the blood clotting process as its features, it may further cause the formation of microthrombus and the damage to chrotoplast, increase the permeability of vessels and induce tissue ischemia and organ dysfunction, which, if not detected and intervened early, might develop into septic shock, multiple organ dysfunction syndrome, or even death.Multiple organ dysfunction syndrome caused by sepsis include acute kidney injury, whose main feature is the decrease of glomerular filtration rate,leading to less urine, no urine, even renal failure. So far, the pathogenesis of AKI caused by sepsis is unclear yet, among which the possible ones are: the hypoperfusion of glomeruli caused by vasodilation, the circulatory disturbances of capillary network around vessels, and the direct damage of infection.In recent years, the dysfunction of kidney tubules induced by oxidative stress is also considered to be an important mechanism.Currently, the remedy to sepsis ranges from antimicrobial management, antiendotoxin management, coagulation disorder rectification, glucocorticoids treatment to nutritional management, but no obvious improvement occurs. Consequently, in-depth research into the pathologic and physiologic change and nosogenesis of AKI caused by sepsis and the exploration of new effective remedy are of great value to treat sepsis and AKI, reducing its death rate.N-acetylcysteine,embodies sulfhedryl group itself so it can restore the disulfide bond in the macromolecule to protect its activity.Therefore it has been widely used in treatment as a gelatinous solvent and then it was found to be of use in the treatment of liver toxic injury.In recent years, N-acetylcysteine, as a sulfhedryl group supplier, has such functions as removing free radicals, anti-infection, regulating cellular metabolism, bettering microcirculation, regulating apoptosis and protecting nucleic acid. Deferoxamine,can reduce the side effects of NAC and the two have synergism effect. Through the experiment of AKI caused by sepsis in the CLP operation on big mouse, the research, with NAC+DFX intervention, check the subjects'blood urea nitrogen,creatinine, malondialdehyde, superoxide dismutase, catalase, myeloperoxidase, glutathione peroxidase, to study the mechanism of action of NAC+DFX in the treatment of AKI caused by sepsis and to assess its preventive and treatment effect, providing new effective treatment to AKI caused by sepsis.ObjectiveTo investigate protective effect of the N-acetyl-cysteine (NAC) combined deferoxamine on renal function in septic rats and whereby the effect of antioxidase imbalance and neutrophile granulocyte infiltration.Methods40 SD rats were divided into 4groups randomly ,there were ten rats in every group.(1) sham group (group A) belly cut right in the middle with caecum exposed and no other measures taken; (2) CLP model group (group B):with caecum ligation perforation(CLP) made; (3) basic treatment group (group C) :hypodermic injection of ceftriaxone (30mg/kg)and clindamycin(20mg/kg)after molding, one shot per 6 hours; (4) treatment of antioxidant group(group D):on the based of group C,hypodermic injection of NAC(20mg/kg) 3, 6, and 12 hours after molding; hypodermic injection of deferoxamin(e20mg/kg) 3 hours after molding。rats in all groups are given hypodermic injection of normal saline(30ml/kg) immediately and 12 hours after molding。To kill all the mousse 12 hours later with blood sample taken to test creatinine(Cr)and usea nitrogen(BUN),and left kidney to test MDA,SOD,CAT,GSH-Px,MPO,and right kidney to examine pathological changes.Resultsglomerular atrophy, glomerular capsule dilatation, tubular epithelial swelling, redness, bleeding, extensive vacuolar degeneration can be found in the kidney's pathological section of group B,these changes significantly improve in group D. apparent decline of group D compared with group B and group C:C[r47.11±9.14 umol/l v(s74.56±11.09 umol/l /67.44±8.40 umol/l)],BUN[11.28±1.43 mmol/l v(s19.70±2.68 mmol/l / 18.31±1.88 mmol/l)].No difference between group D and group A:Cr,BUN(47.11±9.14 umol/l vs 42.20±11.65 umol/l, 11.28±1.43 mmol/l vs 9.98±1.60 mmol/l). In group B, a positive correlation between MDA and Cr(r=0.85,p<0.01) and BUN(r=0.82,p<0.01) and the activity of MPO(r=0.76,p<0.05) is found and no correlation between MDA and SOD/CAT(r=0.36,p>0.05) can be found.ConclusionsExperimental animal model with sepsis Can be successful made by CLP ,Close correlation exists between kidney damage of sepsis and oxidative stress. NAC+DFX has a protective effect on the kidney of rats with sepsis and neutrophile granulocyte infiltration is the main cause for oxidative damage of kidney with sepsis...
Keywords/Search Tags:N-acetyl-cysteine, sepsis, oxidative damage, superoxide, dismutase, catalase
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