Font Size: a A A

Study On Chronic Iron Overload Aggravate Atherosclerosis Of Abdominal Aorta In Gerbils

Posted on:2017-03-21Degree:MasterType:Thesis
Country:ChinaCandidate:W W XuFull Text:PDF
GTID:2284330482495866Subject:Internal medicine
Abstract/Summary:PDF Full Text Request
Background:Cardiovascular diseases were the most important chronic disease, which had affected human health seriously. According to the statistics, nearly 50 percent of people died of cardiovascular diseases and its complications. The number of cardiovascular diseases in our country had been more than 290 million. Cardiovascular disorder, worse than cancer, became the world’s most serious disease with the highest global incidence. Age, hypertension, hyperlipidemia, diabetes and smoking were considered the major risk factors of atherosclerosis. However, more than 50 percent of people who died of coronary heart diseases cannot be explained by theses traditional reasons, which implies more theoretical basis and guidance need for us. In 1980 s, Sullivan first proposed the relationship between iron and cardiovascular disease. Research on iron and cardiovascular diseases never stopped in the past three decades. At present, the relationship between iron overload and atherosclerosis is still controversial, but large number of experiments and epidemiological dates support iron overload associated with atherosclerosis. Iron, as a catalyst, produces large amounts of reactive oxygen species by Fe nton and Haber – Weiss reaction. The overexpress of Reactive oxygen species lead to the occurrence of atherosclerosis by resulting in oxidative damage to biological macromolecules and changing the intracellular redox environment, which eventually affect the intracellular signal transduction pathways and transcription factors.Objective:In order to detect the relationship between chronic iron overload and arteriosclerosis of abdominal aorta in gerbils, we founded the iron- loaded mice model by increasing iron intake artificially. The overexpress of ROS resulted in oxidation-antioxidant out of balance, which closely related with the development of atherosclerosis. According to our experiment, we hope to find new perspectives in clinical prevention and treatment of atherosclerosis.Methods:Select thirty healthy Mongolian gerbils, in 6 and 30 months, randomly divided into 3 groups with 10 rats in each group. The control group included the younger age group(Y-C), ten rats in 6 months, and the elderly control group(E-C), ten rats in 30 months. The study group or the iron overload group was consisted of ten rats in 30 months, which was given iron dextran regularly for 10 weeks. The iron dextran was given days by subcutaneous injection at a dose of 100 mg/ kg with a short interval of 5 days. Then, the gerbils were anesthetized, body weighted, abdominal aortic bled in turn, the heart and abdominal aortas were taken finally.The length of abdominal aorta about 3-5cm. As the experiment was carried out the hearts were weighed by electronic balance, and the blood was isolated with hypothermia high speed centrifugation. The serum, heart and abdominal aorta were kept in hypothermia refrigeration(-80℃).In order to make sure the estab lishment of iron overload model, serum iron and total iron blinding capacity has been measured, at the same time, Prussian blue staining was used to confirm whether the gerbil tissues have iron deposition. The content of MAD and the activity of SOD were examined to study the body balancing status of oxidation and anti-oxidation in gerbils. HE fluorescence staining was used to evaluate oxidative stress injury of Abdominal Aorta in gerbils with chronic iron overload. Von Kossa calcium coloration and O il Red O staining were used to assess the degree of atherosclerotic lesions in different groups of gerbils.Results:1. The content of SI and TIBC in the control group increased by 358% and 110% respectively compared with the elderly control group, and increased by 374% and126% compared with the younger age group. The differences was significant(P<0.01). However, there was no statistically significant difference between the elderly control group(E-C) and the younger age group(Y-C) in serum iron and total iron blinding capacity(P>0.05).2. AS the result shows that: the elderly control group(E-C) compared with the younger age group(Y-C),the content of MDA increased by 28.06%and the activity SOD descended, decreased by 17.44%. The content of MDA and the activity of SOD in the study group(IO-10W) compared with the elderly control group increased by 90.45%and decreased 41.25% respectively. The differences was significant(P<0.05).3. Prussian blue staining shows that the myocardial tissue of the study group has a large number of iron deposition particles, which were stained navy blue by Prussian blue, but, in the control group( including the elder and the younger age group) we didn’t seen iron deposition particle. Compared with the control group the iron deposition areas of the study group increased by 4100 % and the4. Hydroethidine(HE) fluorescence staining was used to detect the express of superoxide anion in abdominal aortic, the brightness represents the expression of superoxide anion. As the results showed the integrated optical density in elder control group brighter than the younger age control group, but, the study group was the darkest. The difference have statistically(P<0.05)5. The O il Red O staining showed that all the animals in the experiment have different degree of dyeing, but, the iron overload group was most obvious. The area of staining and the color depth in the study group more evident than the control group. We used the Image-pro plus 6.0software to analysis the result, which showed that there were statistically significant differences in the rate of positive area between different groups(P<0.05).6. The Von Kossa calcium coloration staining showed the deposit of calcium in artery wall with different degrees in different group. The calcium content in the elderly control group(E-C) increased by 71.7 % compared with the younger age group(Y-C);While the iron overload group increased by 104 % than the elderly control group(E-C).All of them have statistics significance(P<0.01).Conclusion:1、In chronic iron overload condition, excess iron can be deposited in the gerbil tissues.2 、 The excess iron can increase the oxidative stress in gerbils, along with the overexpression of reactive oxygen species.3、Age was the risk factor for abdominal aorta artery plaque, while iron overload make it worse.4、The mechanism of chronic iron overload induced atherosclerosis is likely to be closely related to the increased expression of oxidative stress.
Keywords/Search Tags:Iron overload, abdominal aorta, oxidative stress, atherosclerosis
PDF Full Text Request
Related items