| Arthrosclerosis is common in developed nations. In China, the chance of this epidemic is increasing year after year along with the changes in dietary patterns and improving at standard of living. In addition, a common complication of its heart and cerebrovascular diseases have been middle-aged and elderly groups to the current group of middle-aged even young people, such as myocardial infarction and cerebral ischemic stroke, has been a serious threat to the health of all mankind. Therefore, the depth of its pathogenesis and development of new drugs it is very necessary.The cause of Atherosclerosis is complex and a lot of the mechanism is not yet very clear. At present, people consider it and metabolic syndrome (MS) are closely related. MS is conglomeration of a group of diseases associated with insulin resistance (IR), including abnormal glucose and insulin metabolism, obesity, high cholesterol, hypertension, hyperuricemia and other metabolic disorders body status. In addition, the majority of scholars believe that IR is a central aspect of its pathogenesis and the basic foundation of the disease. Therefore, intervening in the IR effectively be able to slow down atherosclerosis development.In recent years, inflammatory cross responses to atherosclerosis happen, the entire process of development had been brought forward by"response-damage theory". One of, cytokines TNF-αas a pro-inflammatory factor playing a role in many aspects: to promote the creation of endothelin -1 caused by vessel wall injury, the impact of macrophage apoE secretion, increased scavenger receptor activity; to participate in the inflammatory process and cause the blood to promote hypercoagulable state; the impact of insulin receptor phosphorylation and kinase activity, reduced expression of GLUT-4, so that antagonism of insulin and other hormones such as adrenaline caused increased secretion of insulin resistance and hyperinsulinemia, resulting in glucose and lipid metabolism disorders, to promote atherosclerosis the occurrence and development. It can be seen, TNF-αinvolved in IR as the formation and development of one of inflammatory factors, together with the IR to promote atherosclerosis pathogenesis.Thiazolidinediones Rosiglitazone is an insulin sensitizer. it can consider the adoption of the current regulation of lipid metabolism, to improve IR, inhibited TNF-αexpression in the aortic artery and delay the occurrence of atherosclerosis. Rosiglitazone target for peroxisome proliferator-activated receptor (PPAR)-γ. PPAR-γbelong to the nuclear receptor superfamily, the current study found that in fat cell differentiation, glucose metabolism, lipid metabolism and inflammatory response has an important role. We look forward to rosiglitazone in the prevention and treatment of AS play a useful effect.Through this experiment, the affect of rosiglitazone in glucose and lipid metabolism and TNF-αprotein expression have proved that rosiglitazone have effect in regulation of blood lipids, improving IR and inhibiting the role of inflammatory response. rosiglitazone become a new generation of anti- atherosclerosis drugs used clinically to provide a new theoretical basis.MethodsWe selected 37 male Japanese albino rabbits, age 7-8 weeks. All rabbits were randomly divided into three groups: (1) Control group: fed with ordinary fodder 2 times a day; (2) AS group: fed with high fat fodder (120-150g/d) and ordinary fodder; (3) rosiglitazone group: fed with fodder mixed uniformly with rosiglitazone (1.5mg/kg) every morning, then high fat fodder and ordinary fodder. At the beginning of the experiment, we injected the habbits of the last two groups with bovine serum albumin (1g/kg), and the blank group with tales doses of normal saline.We plan the whole experiment time is 14 weeks.At the end of the experiment, we anesthetized rabbits with 10% chloral hydrate, splited the cavitas thoracis and abdominal cavity along the anterior median line, and collected the whole blood from heart. We determined immediately TC, TG, HDL-C, LDL-C, FBG, evaluated blood insulin with radio immunoassay and calculated AI and HOMA-IR. We put out their arteriae aorta and arteria cervicalis which were made into samples. We measured the areas of plaque and total endangium, and calculated the proportion of plaque area to the total endangium area. At the end of the experiment,we applied electron microscope to observe histopathological changes of arteriae aorta and arteria cervicalis.Aortic dissections, specimens made in accordance with the conventional method, stained by the Sudan after measuring plaque area and calculate the percentage ratio of the total area of vascular; by immunohistochemistry methods, X-ray film to observe aortic protein expression of TNF-αlevel and the use of grayscale scan analysis.Results:Retroperitoneal adipose tissue of AS group was more than those of rosiglitazone group. The blood serum of control group appeared transparent, on the contrary, the appearance of the other two groups were ivory white and turbid. The levels of TC, TG, LDL-C and HDL-C of the rosiglitazone group and AS group were higher than those of control group. Compared with AS group, the level of HDL-C of rosiglitazone group was 39.69% higher but levels of TC, TG, LDL-C was lower. Rosiglitazone group FBG, FINS level was significantly lower than that of atherosclerosis, HOMA-IR significantly reduced, reducing the rate of 27.87%.There was not visible atherosclerotic plaque in the arteriae aorta of blank group, through magdala red stain examination. In the arteriae aorta endangium of AS group, we found a large areas of atheromatous plaque extensively, and the proportion of plaque area was 74.7±11.9%. The consequence was different referred to endangium of rosiglitazone group, there was only discontinuous and slight scleratheroma plaque. The proportion of plaque area in rosiglitazone group was 29.9±11.6%, which was lower than that of AS group by 59.9%.Immunohistochemical method through X-ray film to observe aortic TNF-αprotein expression: a blank control group, no positive granules; aorta atherosclerosis group bubble cells, endothelial cells and smooth muscle cells in shading, coloring a high proportion of cells, coloring intensity of the deep, brown tan; rosiglitazone group foam cells and smooth muscle cell shading, but the proportion and intensity of staining were significantly reduced, light brown. Further analysis of each group of aortic TNF-αgrayscale scan result: blank control group, 1.42±0.42, atherosclerosis group 3.87±1.83, rosiglitazone group 1.98±1.44, rosiglitazone group was significantly lower than that of atherosclerosis, reduce as much as 48.8 percent.ConclusionIn this experiment through the injection of heterologous protein and high-fat diet, models of atherosclerosis were created successfully. Compared with AS group, rabbits of rosiglitazone group were in good condition untill the end of experiment.Rosiglitazone group TC, TG, LDL-C and HOMA-IR and atherosclerosis in both groups decreased, and HDL-C increased significantly, these have proved that rosiglitazone have effect in regulation of blood lipids and improving IR. Through the analysis of the results of aortic specimens of Sudan Red staining, suggesting that rosiglitazone may inhibit plaque area. Immunohistochemical method showed that the bubble aorta atherosclerosis group of cells, endothelial cells and smooth muscle cells in shading, coloring a high proportion of cells, staining intensity of a deep brown tan; by rosiglitazone treatment only see the bubble cytoplasmic staining and smooth muscle cells, and the proportion and intensity of staining were significantly reduced Aand became light brown. It proved that rosiglitazone can significantly reduced aortic expression of TNF-αprotein levels. In conclusion, rosiglitazone may prevent atherosclerosis action by regulation of blood lipids, improving insulin resistance and slowing down or reducing the inflammatory response.
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