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The Effects Of PPARgamma Ligand On Ultrastructures Of Renal Artery Endothelium, Expression Of AT1-receptor MRNA And Plasma Angiotensin-Ⅱ In Diabetic Rats

Posted on:2006-08-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y L LuFull Text:PDF
GTID:1104360152993141Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
The incidence of diabetes mellitus is becoming progressively more frequent and the basic pathology of diabetes mellitus is vascularpathy (included microvascular and macrovascular). This is responsible for substantial morbidity and mortality in the diabetic population. Therefore we need know the mechanism of diabetes vascular complication in details. Endothelial is a very important component of blood vessel and it is an active, dynamic tissue. It plays a key role in all stage of arthrosclerosis and controls many important functions, including regulation of vascular tone and maintenance of blood circulation, fluidity, coagulation and inflammatory responses.Renal artery endothelium is very important tissue in diabetes not only as window to observe macro-vascular complication but also as a trigger to be studied the mechanism of that it deteriorates cardiovascular and renal disease. Because renal artery action has tight associated with renin-angiotensin-aldosterone system(RAS). RAS play a pivotal role in both the acute and chronic regulation of systemic arterial pressure, it also is an important modulator of cardiovascular structure and function and may be specifically involved in disease progression. Angiotensin II plays a central role in the regulation of systemic arterial pressure and vascular structure through its systemicsynthesis via the renin-angiotensin-aldosterone cascade.Peroxisome proliferator-activated receptor gamma (PPARgamma) ligand , which it has the same effects as ACEI and ARBs, possesses general beneficial effects on the cardiovascular system but molecular mechanisms for these effects are yet to be fully defined.ObjectivesThe aim of this study is to elucidate (1) How about the changes on renal endothelial ultrastructure in diabetes under scan electric microscope in different time and different gender (2) Whether PPARgamma ligand has ability to correct the vascularpathy in diabetes induced strepozotoncin rats not type-2 diabetes rats? (3) What is the relationship between plasma angiotensin II concentration and renal artery angiotensin II receptorl(ATI) mRNA expression under the condition of renal endothelial destruction? (4) Whether PPARgamma ligand effects on plasma angiotensin II concentration and regular the mRNA expression of ATI-receptor.Materials and MethodsExperimental Animals1. Studies were carried out in 50 Sprague Dawley(SD) rats (male 25 and female 25) 10 weeks old, ( from Zhejiang University Animal Laboratories Center) . Their average weight were 315 ± 30. 06g, average blood sugar were 96±4. 86 mg/L . The rats were housed in animal quarters kept at 20° C to 22℃ with a 12-hour light/dark cycle and were allowed free access to chow and water throughout the study.2. SD rats were divided into two groups: Experimental group treated with intraperitoneal injection dosage of STZ 60mg/kg diluted 0.1M pH 4.5 sodium citrate buffer. Control treated with a single intraperitoneal injection sodiumcitrate buffer 0. 1M, pH 4. 5. We divided them two subgroup that one of sub group raise 6 weeks and another group doeslO weeks. 10 rats In 10 weeks diabetic rats were given PPARgamma ligands: rosiglitazones(ROS)lmg/kg/d intragastric administration(Corporation)dissolved in normal saline.3. Urine glucose were tested every day and glucose was check every week from tail vein for the measurements of glucose (American Adantage). If urine glucose was less than +++(positive reaction), no treatment was given; if urine glucose was about ++++ or more, 1~3 u of protamine zinc insulin was injected subcutaneously to prevent them hyperosmolar or ketoacidosis comma or death.4. After 6 weeks and 10 weeks treatments, rats were anesthetized by intraperitoneal injection of ketamine (35mg/kg)and phenylethylmalonylurea 50mg/kg. About 5ml blood sample was taken from vena cava for the measurements of angotension II concentration respectively. Angiotensin II was analyzed by radio inmmunoassay. The blood glucose was determined with one Touch Blood Glucouse Monitoring system. Exposure rats right renal arteria 1cm and cut in to two same...
Keywords/Search Tags:Diabetes, Renal artery, Endothelial, Angiotensin Ⅱ, AT1-receptor, PPARgamma ligand.
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