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Superior Renoprotective Effects Of The Combination Of Enalapril With Breviscapine And Its Mechanism In Diabetic Rats

Posted on:2007-05-21Degree:MasterType:Thesis
Country:ChinaCandidate:X M QiFull Text:PDF
GTID:2144360185479280Subject:Internal Medicine
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Background and objective: Besides tight glucose control, blockade of the RAS with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) is first-line renoprotective agents in diabetic patients with nephropathy. However, not all patients respond similarly to these treatments. Some patients exhibit a significant beneficial response while others do not. A recent study also has demonstrated that protein kinase C inhibition attenuates the progression of experimental diabetic nephropathy.We have previously reported breviscapine, an inhibitor of PKC, retard the progression of diabetic nephropathy, but this is only partially effective on the ameliorate glomerular pathologies. The present study aimed at the evaluation of the action of the combination of enalapril and breviscapine on oxidative stress, macrophage infiltration and expression of MCP-1, ICAM-1 and TGFβ1 in kidney of diabetic rat induced by STZ.Methods: To induce an experimental model of diabetes, rats received a single intraperitoneal injection of STZ (65mg·kg-1) after uninephrectomy.Fifty adult male Sprague-Dawley rats were randomly separated into five groups: control with no treatment(group C, n=10); diabetes with no treatment(group DM, n=10); diabetes treated with enalapril, at a dose of 10 mg/kg/body weight/day by gavage (group DM+ E, n=10), diabetes treated with breviscapine, at a dose of 20 mg/kg/body weight/day by gavage (group DM+ B, n=10), diabetic rats treated with the combination of both enalapril and breviscapine at the doses described above (group DM+ E+B, n=10). 8 weeks after STZ injection, the following determinations were done in samples: 1. kidney lesions were evaluated using periodic acid-Schiff staining (PAS) staining; 2. plasma glucose (BG) was determined according to standard methods, 24 hours urinary albumin excretion rate (AER) was determined by EIA method; 3. malondiadehyde (MDA), superoxide diamutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px)...
Keywords/Search Tags:Diabetic nephropathy, Enalapril, Breviscapine, Oxidative stress Protein kinase C, Macrophage, Monocyte chemoattractant protein-1, Intercellular adhesion molecule-1, Transforming growth factorβ1
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